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Background: Information related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden. Method: We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights. Results: The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses. Limitations: Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table. Implications: The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the epidemiology characteristics of Herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection in children from January 2018 to December 2023, in Nanjing, China. Methods: We conducted a retrospective analysis of 21,210, 49,494 and 32,457 outpatients and inpatients aged 1 day to 17 years who were subjected to the three herpesviruses (HSV-2, EBV, and CMV) nucleic acid testing from January 2018 to December 2023, respectively. Demographic information, laboratory findings, etc. were collected and analyzed. HSV-2, EBV and CMV nucleic acid testing were performed by real-time PCR. Results: The total rate of detection of the three herpesviruses for all specimens was 0.32% (67/21,210), 14.99% (7419/49,494), and 8.88% (2881/32,457), respectively. A declining trend in the incidence of viral infections over the years was observed for the three herpesviruses (all P<0.05). The detection rate for HSV-2, EBV, and CMV was highest among patients aged 1-3 years, 3-7 years, and 28 days to 1 year, respectively (all P<0.05). The presence of HSV-2 and CMV infection did not exhibit a discernible seasonal pattern, whereas EBV typically demonstrated an elevation during the summer and autumn. Conclusion: EBV and CMV were both prevalent among children in China, except for HSV-2. The annual prevalence of the three herpesviruses show decreasing trend from 2018 to 2023, and no difference in gender (except for EBV). EBV infections usually occur in the summer and autumn, whereas HSV-2 and CMV do not exhibit significant seasonality. The positivity rate of HSV-2 is highest in 1-3 years, EBV is highest in 3-7 years, and that of CMV is highest in 28 days to 1 year. Positive detection rates are higher in outpatients than in inpatients. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of human papillomavirus (HPV) and co-infections with herpes simplex virus type 2 (HSV-2) remains poorly characterized in Africa. High risk HPV (hrHPV) infection is the primary cause of 99.7% all cervical cancer especially in the presence of genital ulcer disease (GUD) which is usually caused by HSV-2. Herpes simplex virus-2 might interact directly with hrHPV to increase the risk of cervical cancer. Co-infection of HPV and HSV-2 in asymptomatic women could provide a clue to early diagnosis of cervical cancer and this could aid in the development of new strategies for effective management and improvement of the quality of life of women who are infected. If the synergy between HPV and HSV-2 can be prevented, there may be significant reduction of the incidence of cervical cancer. Methodology: This was a descriptive cross-sectional study of 515 randomly selected apparently healthy women of reproductive age whose cervical samples were screened for HPV and HSV-2 in Kaduna State, Nigeria. The cervical samples were collected by liquid-based cytology (LBC) for detection of cervical epithelial cell abnormalities (CEA) and molecular detection of HPV and HSV-2 using conventional polymerase chain reaction (PCR) assay. Extracted viral DNAs from the samples were amplified by convectional PCR using specific hrHPV (HPV 16,18, 31 and 45) primer sets and a broad spectrum MY09/11 and GP5+/6+ primers for a wider range of HPV genotypes while HSV-2 DNA was detected by florescence-based PCR assay with HSV-2 gG primers and probes. Results: PCR assay revealed that 14.7% (n=76) of the 515 selected women harbored HPV, HSV-2 or both. The prevalence of HPV, hrHPV, HSV-2 and HPV/HSV-2 co-infection among in the study participants are 11.8% (n=61), 9.3% (n=48), 5.6% 4% (n=29) and 2.3% (n=12) respectively. The frequency of HPV detection in HSV-2 infected participants (41.4%, 12/29) was significantly higher (OR=6.295, p<0.0001) than in HSV-2 negative participants (10.1%, 49/437), but only co-infections of HPV-31 (p=0.004) and HPV-18 (p=0.040) with HSV-2 were significantly associated. Cervical cytology reports on the smears revealed prevalence of cervical epithelial abnormalities (CEA) of 16.7% (n=86), with cervical dysplasia prevalence of 6.4% (n=33), consisting of high grade squamous intraepithelial lesion (HGSIL) of 1.6% (n=8), low grade squamous intraepithelial lesion (LGSIL) of 4.1% (n=21) and atypical squamous cells of uncertain significance (ASCUS) of 0.8% (n=4). The frequency of HPV detection in women with cervical dysplasia (93.9%, 31/33) was significantly higher (OR=14.22, p<0.0001) than in women without cervical dysplasia (6.2%, 30/482), and all HPV genotypes were significantly associated (p<0.05) with cervical dysplasia except HPV 16 (p=0.051). Also, the frequency of HPV/HSV-2 co-infection among women with cervical dysplasia (15.2%, 5/33) was significantly higher than among women without cervical dysplasia (1.5%, 7/482) (OR=12.12, p<0.0001). Comparing women with cervical inflammatory and atrophic changes (n=53), women with cervical dysplasia (HGSIL, LGSIL and ASC-US) had significantly higher frequency of HPV infection (χ²=42.829, p=0.000), HSV-2 infection (χ²=25.140, p=0.001) and HPV/HSV-2 co-infections (χ²=66.602, p=0.000). Conclusion: Co-infection rate of hrHPV and HSV-2 among women in Kaduna State is 2.3%. Demographic factors significantly influencing the rate of co-infections included age and marital status. In spite of the screening method using the traditional Pap smear, GUD and cervical cancer continues to be a major public health problem, thus more sensitive and specific methods such as liquid based cytology technique and polymerase chain reaction for early detection of cervical dysplasia and hrHPV or HSV-2 in asymptomatic women should be adopted for routine use [ABSTRACT FROM AUTHOR]

INTRODUCTION: Neonatal herpes simplex virus (HSV) infection is generally infrequent, despite being a life-threatening illness. Knowledge of its prevalence is limited in Malaysia since most cases are asymptomatic infections and only limited routine neonatal HSV screening is conducted. This study therefore provides a comprehensive investigation of the seroprevalence of HSV-1 and HSV-2 in neonates. MATERIALS AND METHODS: Serological screening for HSV-1 IgG and HSV-2 IgG antibody tests using the Electrochemiluminescence assay was performed on serum samples of 215 neonates delivered from January until December 2022 at Hospital Universiti Sains Malaysia. RESULTS: Of the neonates, 54.4% were found to be HSV-1 positive, while 4.2% were HSV-2 positive. All the HSV-2 neonates were co-infected with HSV-1. Newborns aged 0-10 days were the most infected group by HSV-1 (92.3%) and HSV-2 (55.6%). The most reported clinical presentation was small gestational age (SGA) (60%). Microcephaly and macrocephaly were observed in one neonate each. The clinical presentations of reactive HSV-1 and HSV-2 cases revealed the presence of fever with rash in both cases. CONCLUSION: The high seroprevalence of HSV-1 is alarming. It is hoped that these data will support the advocacy of screening women for HSV before or during pregnancy as a precautionary approach to reducing the risk of vertical transmission. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus, the cause of genital herpes, and its infection can increase the risk of HIV-1 infection. After initial infection, HSV-2 can establish lifelong latency within the nervous system, which is likely associated with the virus-mediated immune evasion. In this study, we found that HSV-2 UL24 significantly inhibited the activation of the IFN-β promoter and the production of IFN-β at both mRNA and protein levels. Of importance, the inhibitory effect of HSV-2 on IFN-β production was significantly impaired in the context of HSV-2 infection when UL24 was knocked down. Additional studies revealed that, although the full-length HSV-2 UL24 affected cell cycle and viability to some extent, its N-terminal 1–202AA domain showed no obvious cytotoxicity while its C-terminal 201–281 AA domain had a minimal impact on cell viability. Further studies showed that the N-terminal 1–202 AA domain of HSV-2 UL24 (HSV-2 UL24-N) was the main functional region responsible for the inhibition of IFN-β production mediated by HSV-2 UL24. This domain significantly suppressed the activity of RIG-IN, MAVS, TBK-1, IKK-ε, or the IRF-3/5D-activated IFN-β promoter. Mechanistically, HSV-2 UL24-N suppressed IRF-3 phosphorylation, resulting in the inhibition of IFN-β production. The findings of this study highlight the significance of HSV-2 UL24 in inhibiting IFN-β production, revealing two potential roles of UL24 during HSV-2 infection: facilitating immune evasion and inducing cell cycle arrest. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity, and, primarily, the growing problem of drug resistance. Here, we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of the virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles impairing virus absorption and penetration was shown. The toxicity profile proved to be extremely good, with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against acyclovir (ACV)-resistant HSV isolates, while HSV subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment. [ABSTRACT FROM AUTHOR]

Human herpes viruses (HHV) are ubiquitous and have been implicated in numerous long-term health conditions. Since the association between viral exposure and long-term health impacts is partially influenced by variation in human leukocyte antigen (HLA) genes, we evaluated in silico the binding affinities of 9 HHV envelope glycoproteins with 127 common HLA Class I and Class II molecules. The findings show substantial variability in HHV binding affinity across viruses, HLA Class, HLA genes, and HLA alleles. Specific findings were as follows: (1) the predicted binding affinities of HHVs were characterized by four distinct groupings—[HHV1, HHV2], [HHV3, HHV4, HHV5], [HHV6A], [HHV6B, HHV7, HHV8]—with relatively lower binding affinities for HHV1, HHV2, and HHV6a compared to other HHVs; (2) significantly higher binding affinity was found for HLA Class I relative to Class II; (3) analyses within each class demonstrated that alleles of the C gene (for Class I) and DRB1 gene (for Class II) had the highest binding affinities; and (4) for each virus, predicted binding affinity to specific alleles varied, with HHV6a having the lowest affinity for HHV-HLA complexes, and HHV3, HHV4, and HHV5 having the highest. Since HLA-antigen binding is the first step in initiating an immune response to foreign antigens, these relative differences in HHV binding affinities are likely to influence long-term health impacts such that the cells infected with viruses associated with higher binding affinities across common HLA alleles may be more reduced in numbers, thereby lowering the potential for long-term sequelae of their infections. [ABSTRACT FROM AUTHOR]

This document contains a collection of four case reports that provide insights into various liver diseases. The first report focuses on the prevalence of intestinal failure-associated liver disease (IFALD) in patients receiving long-term home parenteral nutrition (HPN), identifying ongoing HPN and short gut syndrome as predictors for IFALD. The second report introduces a predictive model called the Portal Decompensation Score (PDS), which accurately predicts portal hypertension-related decompensation events in cirrhosis patients. The third report describes a quality improvement project aimed at enhancing the assessment of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes in primary care. Lastly, the fourth report presents a case of hepatosplenic candidiasis in a non-neutropenic patient following endoscopic cholangiopancreatography (ERCP). These case reports offer valuable information on the diagnosis, management, and outcomes of different liver diseases. [Extracted from the article]

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9–14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2. Author summary: Herpes simplex virus 2 (HSV-2) is a cause of genital herpes, neonatal herpes, and herpes encephalitis. The virus persists in the nervous system for life and periodically reactivates resulting in recurrent genital lesions and can be transmitted to susceptible individuals. Currently there is no cure for the disease and no licensed vaccine to prevent infection. Numerous HSV-2 vaccine candidates have been tested in animal models, mostly in mice and guinea pigs, and vaccine efficacy observed in these animals has been poorly predictive for effectiveness of HSV-2 vaccines in humans. Thus, there is a need for an animal model that better recapitulates human disease and is more predictive for the efficacy of prophylactic vaccines. We evaluated an HSV-2 genital infection model using Cebus apella, a New World primate. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9–14 days after intravaginal inoculation. The animals developed symptoms similar to most humans with genital vesicular lesions and no neurological signs. They also developed antibody and T cell responses to HSV-2. Prior infection generally reduced reinfection. These observations suggest that Cebus apella monkeys have the potential to serve as a good model for evaluating the efficacy of prophylactic HSV-2 vaccines. [ABSTRACT FROM AUTHOR]

Background: Aseptic meningitis comprises meningeal inflammation and cerebrospinal fluid (CSF) pleocytosis without positive Gram stain and culture. Regional differences exist in the prevalence of viral etiologies of aseptic meningitis. We aimed to assess the etiologies of aseptic meningitis in immunocompetent adults, focusing on herpes simplex virus type 2 (HSV-2). Methods: This study retrospectively analyzed immunocompetent adults diagnosed with meningitis at a Korean tertiary care hospital from 2016 to 2018. Aseptic meningitis was defined through clinical and CSF analysis. We compared clinical and laboratory characteristics across viral etiologies and investigated predictors of HSV-2 meningitis. Results: A total of 98 patients (46.9% female) with aseptic meningitis were finally enrolled. The etiologies of aseptic meningitis were identified in 62 patients (63.3%), including enterovirus (28.5%), HSV-2 (16.3%), and varicella zoster virus (VZV, 15.3%). HSV-2 showed female predominance, with shorter admission times with longer hospital stays and a recurrent meningitis history. Compared to other viral etiologies, HSV-2 showed higher CSF white blood cell (WBC) counts and protein levels but lower C-reactive protein (CRP) levels. A random forest model identified previous meningitis history and serum CRP level as key predictors of HSV-2 meningitis. Conclusions: This study provides insights into the etiologies of aseptic meningitis in a specific Korean region, identifying HSV-2 as a notable cause. The prediction model suggested that the clinical history of previous meningitis and serum CRP level may guide clinical assessment of meningitis. [ABSTRACT FROM AUTHOR]

Background: Functionalized nanoparticles (NPs) represent a cutting edge in innovative clinical approaches, allowing for the delivery of selected compounds with higher specificity in a wider time frame. They also hold promise for novel theranostic applications that integrate both diagnostic and therapeutic functions. Pathogens are continuously evolving to try to escape the strategies designed to treat them. Objectives: In this work, we describe the development of a biotechnological device, Nano-Immuno-Probes (NIPs), for early detection and infections treatment. Human Herpes Simplex Virus 2 was chosen as model pathogen. Methods: NIPs consist of PLGA-PEG-Sulfone polymeric NPs conjugated to recombinant Fab antibody fragments targeting the viral glycoprotein G2. NIPs synthesis involved multiple steps and was validated through several techniques. Results: DLS analysis indicated an expected size increase with a good polydispersity index. Z-average and z-potential values were measured for PLGA-PEG-Bis-Sulfone NPs (86.6 ± 10.9 nm; –0.7 ± 0.3 mV) and NIPs (151 ± 10.4 nm; −5.1 ± 1.9 mV). SPR assays confirmed NIPs' specificity for the glycoprotein G2, with an apparent KD of 1.03 ± 0.61 µM. NIPs exhibited no cytotoxic effects on VERO cells at 24 and 48 h. Conclusions: This in vitro study showed that NIPs effectively target HSV-2, suggesting the potential use of these nanodevices to deliver both contrast agents as well as therapeutic compounds. [ABSTRACT FROM AUTHOR]

Autophagy, an evolutionarily conserved cellular process, influences the regulation of viral infections. While the existing understanding indicates that Herpes Simplex Virus type 2 (HSV-2) maintains a basal level of autophagy to support its viral yield, the precise pathways governing the induction of autophagy during HSV-2 infection remain unknown. Therefore, this study aims to explore the role of type I interferons (IFN-I) in modulating autophagy during HSV-2 infection and to decode the associated signaling pathways. Our findings revealed an interplay wherein IFN-I regulates the autophagic response during HSV-2 infection. Additionally, we investigated the cellular pathways modulated during this complex process. Exploring the intricate network of signaling events involved in autophagy induction during HSV-2 infection holds promising therapeutic implications. Identifying these pathways advances our understanding of host–virus interactions and holds the foundation for developing targeted therapeutic strategies against HSV-2. The insight gained from this study provides a platform for exploring potential therapeutic targets to restrict HSV-2 infections, addressing a crucial need in antiviral research. [ABSTRACT FROM AUTHOR]

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that causes a persistent infection in sensory ganglia. The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection. [ABSTRACT FROM AUTHOR]

Background: This study assesses the prevalence of sexually transmitted infections (STIs) in first time visitors to the STIs clinic in Hangzhou, China, considering different genders, ages and symptoms. And also explores howthe COVID‐19 pandemic has affected on STIs. Methods: From 2019 to 2023, 27,283 first time visitors were tested for nine distinct STIs, including Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), syphilis, Herpes Simplex Virus type 2 (HSV‐2), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and vaginal Candida. Results: Symptomatic male and female visitors showed overall STI‐positive rates of 39.27% and 59.20%, respectively(p <.001). The top three pathogens in both genders were HPV (47.56% and 56.71%), UU (29.21% and 56.47%), and HSV‐2 (22.41% and 52.94%). Among asymptomatic visitors, the total STI‐positive rate was 36.63% in males and 52.03% in females. Age‐stratified analysis revealed higher STI rates in visitors ≤ 20 or >50 years, regardless of gender and symptoms. During the COVID‐19 pandemic, symptomatic visitors showed lower positive rates for HPV, HIV, syphilis, and HSV‐2, while Candida, UU, CT, NG, and multiple infections increased. Among asymptomatic visitors, HPV had the lowest positive rate, while NG and multiple infections increased during the pandemic. Conclusion: STI prevalence is notably high, particularly in those aged ≤ 20 and >50 years. It emphasizes the need for enhanced health education, condom use, and vaccination. The COVID‐19 pandemic impacting STIs through varied factors, such as reduced sexual activity and clinical service interruption. [ABSTRACT FROM AUTHOR]

The multifunctional tegument protein pUL21 of HSV-2 is phosphorylated in infected cells. We have identified two residues in the unstructured linker region of pUL21, serine 251 and serine 253, as phosphorylation sites. Both phosphorylation sites are absent in HSV-1 pUL21, which likely explains why phosphorylated pUL21 was not detected in cells infected with HSV-1. Cells infected with HSV-2 strain 186 viruses deficient in pUL21 phosphorylation exhibited reductions in both cell-cell spread of virus infection and virus replication. Defects in secondary envelopment of cytoplasmic nucleocapsids were also observed in cells infected with viruses deficient in pUL21 phosphorylation as well as in cells infected with multiple strains of HSV-2 and HSV-1 deleted for pUL21. These results confirm a role for HSV pUL21 in the secondary envelopment of cytoplasmic nucleocapsids and indicate that phosphorylation of HSV-2 pUL21 is required for this activity. Phosphorylation of pUL21 was substantially reduced in cells infected with HSV-2 strain 186 mutants lacking the viral serine/threonine kinase pUL13, indicating a requirement for pUL13 in pUL21 phosphorylation. IMPORTANCE It is well known that post-translational modification of proteins by phosphorylation can regulate protein function. Here, we determined that phosphorylation of the multifunctional HSV-2 tegument protein pUL21 requires the viral serine/threonine kinase pUL13. In addition, we identified serine residues within HSV-2 pUL21 that can be phosphorylated. Phenotypic analysis of mutant HSV-2 strains with deficiencies in pUL21 phosphorylation revealed reductions in both cell-cell spread of virus infection and virus replication. Deficiencies in pUL21 phosphorylation also compromised the secondary envelopment of cytoplasmic nucleocapsids, a critical final step in the maturation of all herpes virions. Unlike HSV-2 pUL21, phosphorylation of HSV-1 pUL21 was not detected. This fundamental difference between HSV-2 and HSV-1 may underlie our previous observations that the requirements for pUL21 differ between HSV species. [ABSTRACT FROM AUTHOR]

Alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV), infect a diverse array of hosts, spanning both humans and animals. Alphaherpesviruses have developed a well-adapted relationship with their hosts through long-term evolution. Some alphaherpesviruses exhibit a typical neurotropic characteristic, which has garnered widespread attention and in-depth research. Virus latency involves the retention of viral genomes without producing infectious viruses. However, under stress, this can be reversed, resulting in lytic infection. Such reactivation events can lead to recurrent infections, manifesting as diseases like herpes labialis, genital herpes, and herpes zoster. Reactivation is a complex process influenced by both viral and host factors, and identifying how latency and reactivation work is vital to developing new antiviral therapies. Recent research highlights a complex interaction among the virus, neurons, and the immune system in regulating alphaherpesvirus latency and reactivation. Neurotropic alphaherpesviruses can breach host barriers to infect neurons, proliferate extensively within their cell bodies, and establish latent infections or spread further. Whether infecting neurons or spreading further, the virus undergoes transmission along axons or dendrites, making this process an indispensable part of the viral life cycle and a critical factor influencing the virus's invasion of the nervous system. Research on the transmission process of neurotropic alphaherpesviruses within neurons can not only deepen our understanding of the virus but can also facilitate the targeted development of corresponding vaccines. This review concentrates on the relationship between the transmission, latency, and activation of alphaherpesviruses within neurons, summarizes recent advancements in the field, and discusses how these findings can inform the design of live virus vaccines for alphaherpesviruses. [ABSTRACT FROM AUTHOR]

Background: Cervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions. Case presentation: A 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae. There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms. Conclusion: Herpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment. [ABSTRACT FROM AUTHOR]

Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 μM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to determine the etiological, sociodemographic, and clinical characteristics of STIs, and the level of resistance in M. genitalium in Shenzhen, a representative first-tier city of southern China. Methods: A multicenter cross-sectional study was conducted and 7886 sexually active participants attending STI-related departments were involved from 22 hospitals. Nine STI-related organisms including N. gonorrhoeae, C. trachomatis, T. vaginalis, M. genitalium, HSV-1, HSV-2, M. hominis, U. parvum, and U. urealyticum were screened. Results: Being single or divorced was associated with increased detection of N. gonorrhoeae, C. trachomatis, M. genitalium, HSV-1, HSV-2 and M. hominis. Lower education level was associated with increased detection of C. trachomatis, HSV-2 and M. hominis. No insurance coverage was an independent risk factor for T. vaginalis, M. hominis and U. parvum positivity. Three resistance-determining regions related to macrolide and fluoroquinolone were sequenced in 154 M. genitalium positive samples, among which 90.3% harbored mutations related to macrolide or fluroquinolone resistance and 67.5% were multidrug-resistant M. genitalium. A2072G in 23S rRNA and Ser83Ile in parC were the most common mutations. M. hominis was associated with manifestations of bacterial vaginosis in female and epididymitis in male. Conclusions: Single or divorced individuals, those with lower education level and individuals without insurance are higher-risk key populations for STIs. The prevalence of antimicrobial-resistant M. genitalium in Shenzhen is high. Detection of M. hominis increased significantly with lower education level and no health insurance coverage, and it is associated with bacterial vaginosis or epididymitis, indicating that M. hominis deserves further attention. [ABSTRACT FROM AUTHOR]

The impact of viral keratitis (VK) on individuals and society is notable. Early diagnosis and treatment are crucial in managing viral keratitis effectively. Timely intervention with antiviral medications and supportive care can help mitigate the severity of the infection and improve visual outcomes. We examined the prevalence of varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), adenovirus (AdV) and herpes simplex virus type 2 (HSV-2) in patients suspected for ocular infections. Patients included in the study exhibited various clinical manifestations indicative of ocular pathology, such as infectious keratitis, corneal scar, endogenous endophthalmitis, panuveitis, endothelitis, stromal edema, and other relevant conditions. Four different types of tear fluid, corneal samples epithelium, aqueous humor and vitreous humor were taken. After genome extraction, multiplex real-time PCR was used for diagnosis of viruses. 48 (29.6%) out of the total of 162 (100%) eye specimen were positive. The dominant prevalence was VZV (12.3%) and HSV-1 (11.7%) followed by AdV (4.9%) and HSV-2 (0.6%). There were 4 (8.3%) coinfections within the samples (HSV-1 and VZV). Aqueous humor samples demonstrated superior virus detection ability and our only HSV-2 positive sample was from aqueous humor. The utilization of multiplex real-time PCR assays in differential diagnosis of VK holds promise for expeditious diagnoses while also preventing unwarranted antibiotic prescriptions. Moreover, the aqueous humor appears to be a more sensitive site for detecting viral keratitis. [ABSTRACT FROM AUTHOR]

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated. [ABSTRACT FROM AUTHOR]

The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl− channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5–20 μM), CFTRi-172 (5–20 μM) and IOWH-032 (5–20 μM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10–20 μM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl− concentration ([Cl−]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 μM) increased the reduced [Cl−]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments. [ABSTRACT FROM AUTHOR]

Coridothymus capitatus is a perennial herb with aromatic leaves and flowers, distinct from Thymus vulgaris in its chemical composition, resulting in a unique Thymus Essential Oil (TEO). A main component of TEO, carvacrol, is known for its antimicrobial and insecticidal activity. Carvacrol has potent antibacterial, antioxidant, anti-inflammatory, and antifungal properties, generating interest in traditional medicine. However, studies on its antiviral activity are limited. Given the rise in viral infections and limitations of synthetic antiviral drugs, natural antiviral agents are promising due to their efficacy, lower resistance development, and reduced side effects. This study assessed the antiviral efficacy of TEO compared to that of pure carvacrol. We tested various viruses, revealing significant inhibitory effects of TEO on the replication of only Simplexvirus humanalpha1 (HSV-1) and Simplexvirus humanalpha2 (HSV-2), with specific interference during the early stages of the viral replication cycle after the adsorption period. TEO exhibited inhibitory effects at doses below the cytotoxic threshold, with IC50 values of 47 μg/mL for HSV-1 and 40 μg/mL for HSV-2. Maximum virus inhibition was achieved when TEO was added within 90 min post-infection, indicating interference with early viral replication steps. These findings highlight the potential of TEO as a natural antiviral agent and suggest further research into its mechanisms and clinical applications. [ABSTRACT FROM AUTHOR]

Background: The rising prevalence of herpes simplex type 2 (HSV-2) infection poses a growing global public health challenge. A comprehensive understanding of its epidemiology and burden disparities in China is crucial for informing targeted and effective intervention strategies in the future. Methods: We followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 31st, 2024. We synthesized HSV-2 seroprevalence data across different population types. We used random-effects models for metaanalyses and conducted meta-regression to assess the association between population characteristics and seroprevalence. Results: Overall, 23,999 articles were identified, and 402 publications (1,203,362 participants) that reported the overall seroprevalence rates (858 stratified measures) were included. Pooled HSV-2 seroprevalence among the general population (lower risk) was 7.7% (95% CI: 6.8-8.7%). Compared to the general population, there is a higher risk of HSV-2 prevalence among intermediate-risk populations (14.8%, 95% CI: 11.0-19.1%), and key populations (31.7%, 95% CI: 27.4-36.1%). Female sexual workers (FSWs) have the highest HSV-2 risk (ARR:1.69, 95% CI: 1.61-1.78). We found northeastern regions had a higher HSV-2 seroprevalence than other regions (17.0%, 95% CI: 4.3-35.6%, ARR: 1.38, 95% CI: 1.26-1.50, Northern China as the reference group). This highlighted the disparity by population risk levels and regions. We also found lower HSV-2 prevalence estimates in publications in Chinese bibliographic databases than those in English databases among key populations (such as MSM and HIVdiscordant populations). Conclusion: There is a gradient increase in HSV-2 prevalence risk stratification. We also identified region, population, and age disparities and heterogeneities by publication language in the HSV-2 burden. This study provides guidance for future HSV-2 prevention to eliminate disparities of HSV-2 infection and reduce overall HSV-2 burden. [ABSTRACT FROM AUTHOR]

To assess the accuracy of HSV1and HSV2 antibody testing in identifying genital herpes infection. Methods: A cohort of 299 patients previously diagnosed with recurrent genital herpes, confirmed via PCR, were tested using ELISA for HSV1 and HSV2 IgM and IgG antibodies. The study compared the accuracy of HSV1 and HSV2 antibody tests in diagnosing genital herpes. Results: Among 299 patients, 14 tested positives for HSV1 DNA. Of these, 9 had HSV1 IgG antibodies, but none had HSV2 IgG antibody. Among 278 patients with HSV2 DNA, 149 had HSV1 IgG, 9 had HSV2 IgG, and 97 had both. Seven patients had both HSV1 and HSV2 DNA; 3 had HSV1 IgG, 1 had HSV2 IgG, and 3 had both. The accuracy of HSV1 IgG for HSV1 infection was 64.2%, and for HSV1 and HSV2 co-infection, 85.7%. The accuracy of HSV2 IgG for HSV2 infection was 38.1%, and for HSV1 and HSV2 co-infection, 57.1%. The combined antibody positivity accuracy was 34.9%. Conclusion: Genital herpes is primarily caused by HSV2 (92.98%). A smaller percentage is HSV1 (4.67%) or co-infection (2.34%). Despite relatively low diagnostic accuracy (34.9– 85.7%) for antibody detection, combined antibody testing is necessary. Herpes DNA testing is recommended for accurate diagnosis. Absence of antibodies does not rule out genital herpes and clinical assessment is essential. [ABSTRACT FROM AUTHOR]

Background: The current prevalence of Herpes simplex virus type 2 (HSV-2) infection is notably high, with individuals afflicted by HSV-2 facing recurrent outbreaks, challenges in achieving remission, and an elevated risk of HIV infection. This study aims to investigate the relationship between alcohol consumption and HSV-2 infection. Methods: The data for this study were sourced from 7257 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. The target population consisted of adults with reliable HSV-2 plasma results, and alcohol consumption was assessed using self-report methods. We evaluated the odds ratio (OR) and 95% confidence interval (CI) for the association between alcohol consumption and HSV-2 infection. These estimations were derived from a logistic regression model that was adjusted for key confounding factors. Subgroup analysis specifically focused on alcohol consumption, and the interaction between HSV-2 infection, alcohol consumption, and other variables was assessed through stratified analysis. Results: Among the 7,257 participants included, 89.8% (6,518/7,257) reported varying levels of alcohol consumption history. Compared to individuals who never drinkers, the adjusted odds ratios (ORs) for former drinkers, light drinkers, moderate drinkers, and heavy drinkers were 1.79 (95% CI: 1.34–2.4, p < 0.001), 1.38 (95% CI: 1.07–1.77, p = 0.012), 1.49 (95% CI: 1.15–1.94, p = 0.003), and 1.47 (95% CI: 1.14–1.9, p = 0.003), respectively. The results remained stable in subgroup analyses and sensitivity analyses. Conclusion: Current research indicates that individuals with a history of alcohol consumption exhibit a higher risk of HSV-2 infection compared to those who have never drinkers. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions The underlying pathogenesis of pityriasis lichenoides et varioliformis acuta (PLEVA) remains unclear, although immunologic injury and viral etiology have been suggested.To evaluate and expand the immunophenotype of PLEVA and to search for possible viral pathogens.Formalin‐fixed, paraffin‐embedded specimens of 20 patients with PLEVA and 9 patients with common inflammatory dermatoses (ID) were studied for immunophenotyping and for human herpesvirus (HHV) 1 and 2, cytomegalovirus (CMV), HHV‐8, parvovirus B19, and Epstein–Barr virus (EBV) immunohistochemistry. The presence of HHV‐6, HHV‐7, and enteroviruses was assayed molecularly.The numbers of CD8+ T cells and T‐cell intracellular antigen‐1 (TIA‐1)+ cells were statistically significantly higher in PLEVA compared to the ID group. Immunohistochemistry for human HHV‐1 and HHV‐2, CMV and HHV‐8, parvovirus B19, and in situ hybridization for EBV were all negative. There was molecular evidence for HHV‐7 in only one PLEVA case (5%). Molecular studies for HHV‐6 and enterovirus involvement were negative in all the PLEVA specimens.The predominant T‐cell infiltrate in PLEVA is dominated by CD8+ cells, and by increased numbers of TIA1+ cells, which may indicate a cytotoxic T‐cell damage to the epidermis. Viral presence was not detected. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis.A case series was constructed by reviewing medical records.Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis.Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered. [ABSTRACT FROM AUTHOR]

Background: Various microbes and allergens are responsible to cause keratoconjunctivitis. But the viral agents are mostly associated with this ocular illness. Adenovirus, Herpes simplex virus (HSV), and enterovirus are the main causative agents. Among those, HSV is of great concern as it can lead to encephalitis. Aim: To determine the prevalence and know the circulating genotype of Herpes Virus among the population of Andaman Island. Methods: Conjunctival swabs from 470 Keratoconjunctivitis suspects were collected (August 2017-January 2022). Diagnosis of HSV-1 and HSV-2 carried out by PCR. Result: Positives were typed with Sanger's Sequencing and sequences analyzed with MEGA software. 20 patients found positive for HSV-1 and typing revealed HSV Strain circulating in Andaman Islands was of AES origin. Conclusion This is first report on Ocular HSV prevalence and strain connected to AES origin in Andaman Islands. To prevent encephalitis epidemics in Andaman population, HSV screening for cases is needed. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex type 2 is a common infection worldwide. This disease is common in both developed and developing countries. Early detection of infection is very important to reduce the risk of infection. Real-time reliable PCR is a very sensitive and specific method that can be used as the best marker in determining the therapeutic effect by identifying a viral genome in an individual. The prevalence of herpes simplex virus type 2 in women with genital herpes was evaluated by Real time PCR method. Methods: From January 1999 to March 2010, 45 samples of vaginal swabs and cervix of women with genital herpes were examined for HSV virus DNA detection using Real Time PCR. Results: The mean age of the patients was 35.9 + 5.9. The percentage of positive cases of herpes simplex virus type 2 in the studied women was 22.2% and the history of infection with hpv was 33.3% vs. 12.5%. = 0.094 which was significant. Conclusion: Clinical specimens of vaginal swabs from genital herpes caused by herpes simplex virus 2 can be quantitatively analyzed instead of nucleic acid extraction and amplification by PCR. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20–25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies. [ABSTRACT FROM AUTHOR]

Mollaret's meningitis is a rare neurological disorder characterized by recurrent episodes of aseptic lymphocytic meningitis, often associated with herpes simplex virus 2 (HSV-2) infection. We report the case of a 39 y.o. Italian woman who experienced four episodes of aseptic lymphocytic meningitis between 2004 and 2023, diagnosed as Mollaret's meningitis. In each episode, the patient presented with fever, severe headache and photophobia. In two episodes cutaneous vesicles in the left gluteal area preceding meningitis symptoms were also reported. A diagnostic evaluation included a physical–chemical analysis and a real-time PCR of the cerebrospinal fluid (CSF). The CSF presented pleocytosis with lymphocytic predominance and a positive HSV-2 load, with a peak of 1234 copies/mL. The patient was treated successfully with acyclovir, and the symptoms resolved without neurological sequelae. This case highlights the importance of comprehensive diagnostic testing and vigilant monitoring to manage Mollaret's syndrome effectively. [ABSTRACT FROM AUTHOR]

Residues ASN94 and GLN41 presented the highest frequency in molecular docking tests. The geraniin-glycoprotein D(gD) complexes was stable with RMSD(root mean square deviation)value less than 0.3 nm. The Molecular dynamic (MD) simulations revealed stable hydrogen bonds between gD and geraniin. Root mean square fluctuation (RMSF) values were less than 0.15 nm around the interface of geraniin-gD complex. In virucidal assays showed a much higher anti-HSV-2 inhibition activity of geraniin as compared to acyclovir(ACV).Human immunodeficiency virus transactivator (HIV-TAT) treatment significantly enhanced HSV-2 replication and lethal effect on HaCaT cells. The inhibitory rate of geraniin against HSV-2 coinfected with HIV-TAT was significantly decreased. The immunofluorescence results also revealed that HSV-2 gD expression presented a green fluorescence on HaCaT cells membranes and showed clear downregulation in geraniin-treated cells, but was expressed clearly on cell membranes under geraniin, HSV-2 and HIV-TAT cotreatment. The anti-apoptotic effect from geraniin persisted after 72 h, while the anti-apoptotic effect from geraniin diminished when HIV-TAT and geraniin were combined. [ABSTRACT FROM AUTHOR]

TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16–45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005–2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections. [ABSTRACT FROM AUTHOR]

Herpes simplex virus 2 (HSV-2) is a sexually transmitted infection affecting 491 million individuals globally. Consequently, there is a great need for both prophylactic and therapeutic vaccines. Unfortunately, several vaccine clinical trials, primarily employing the glycoprotein D of HSV-2 (gD-2), have failed. The immune protection conferred by human anti-HSV-2 antibodies in genital infection and disease remains elusive. It is well-known that gD-2 elicits cross-reactive neutralizing antibodies, i.e., anti-gD-2 antibodies recognize gD in HSV-1 (gD-1). In contrast, anti-glycoprotein G in HSV-2 (mgG-2) antibodies are exclusively type-specific for HSV-2. In this study, truncated versions of gD-2 and mgG-2 were recombinantly produced in mammalian cells and used for the purification of anti-gD-2 and anti-mgG-2 antibodies from the serum of five HSV-2-infected subjects, creating a pool of purified antibodies. These antibody pools were utilized as standards together with purified mgG-2 and gD-2 antigens in ELISA to quantitatively estimate and compare the levels of cross-reactive anti-gD-1 and anti-gD-2 antibodies, as well as anti-mgG-2 antibodies in sera from HSV-1+2-, HSV-2-, and HSV-1-infected subjects. The median concentration of anti-mgG-2 antibodies was five times lower in HSV-1+2-infected subjects as compared with cross-reactive anti-gD-1 and anti-gD-2 antibodies, and three times lower in HSV-2 infected subjects as compared with anti-gD-2 antibodies. The pool of purified anti-gD-2 antibodies presented neutralization activity at low concentrations, while the pool of purified anti-mgG-2 antibodies did not. Instead, these anti-mgG-2 antibodies mediated antibody-dependent cellular cytotoxicity (ADCC) by human granulocytes, monocytes, and NK-cells, but displayed no complement-dependent cytotoxicity. These findings indicate that antibodies to mgG-2 in HSV-2-infected subjects are present at low concentrations but mediate the killing of infected cells via ADCC rather than by neutralizing free viral particles. We, and others, speculate that Fc-receptor mediated antibody functions such as ADCC following HSV-2 vaccination may serve as a better marker of protection correlate instead of neutralizing activity. In an mgG-2 therapeutic vaccine, our findings of low levels of anti-mgG-2 antibodies in HSV-2-infected subjects may suggest an opportunity to enhance the immune responses against mgG-2. In a prophylactic HSV-2 mgG-2 vaccine, a possible interference in cross-reactive immune responses in already infected HSV-1 subjects can be circumvented. [ABSTRACT FROM AUTHOR]

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans. [ABSTRACT FROM AUTHOR]

Men who have sex with men (MSM) have high incidence rates of HIV infection worldwide. Voluntary medical male circumcision (VMMC) reduces HIV risk for men who have sex with women, but whether it is an effective strategy for MSM remains uncertain. This randomized controlled trial assessed the efficacy of VMMC in preventing incident HIV infection among MSM in China at a time when preexposure prophylaxis was not routinely offered or used. Visual Abstract. Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men: Men who have sex with men (MSM) have high incidence rates of HIV infection worldwide. Voluntary medical male circumcision (VMMC) reduces HIV risk for men who have sex with women, but whether it is an effective strategy for MSM remains uncertain. This randomized controlled trial assessed the efficacy of VMMC in preventing incident HIV infection among MSM in China at a time when preexposure prophylaxis was not routinely offered or used. Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. Design: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436) Setting: 8 cities in China. Participants: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. Intervention: VMMC. Measurements: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. Results: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P  = 0.029), and the HIV incidence was lower in the intervention group (log-rank P  = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. Limitation: Few HIV seroconversions and limited follow-up period. Conclusion: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. Primary Funding Source: The National Science and Technology Major Project of China. [ABSTRACT FROM AUTHOR]

The third edition of the "Virus–Host Interaction" series showcases 12 research articles that delve into the intricate dynamics between viruses and their host organisms. Studies range from exploring antiviral therapies to investigating the molecular mechanisms of SARS-CoV-2 infection and the zoonotic potential of viruses. The edition also highlights the role of the kallikrein–kinin system in viral infections, immune responses to Dengue virus, viral immune evasion strategies, and potential therapeutic targets for inhibiting viral proliferation. Overall, the research presented underscores the importance of ongoing efforts in virology to address current viral threats and prepare for future challenges. [Extracted from the article]

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases. [ABSTRACT FROM AUTHOR]

Background: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). Methods and findings: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. Conclusions: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO number: CRD42022348045. Julia Michalow and colleagues estimate the aetiologies and aetiologic distributions of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa. Author summary: Why was this study done?: Symptom-based case management is common for treating sexually transmitted infections (STIs) in sub-Saharan Africa (SSA). Characterising the infectious aetiologies (causes) of each syndrome is crucial to ensure adequate choice of treatment. Recent comprehensive assessments on the aetiologies for vaginal discharge, urethral discharge, and genital ulcer are lacking in SSA. What did the researchers do and find?: We conducted a systematic review that included 190 studies in 32 SSA countries spanning 1969 and 2022. We accounted for the sensitivity and specificity of different diagnostic tests used across studies and used meta-regression models to estimate the distribution of infections causing each symptom. We determined that the main aetiologies for vaginal discharge were candidiasis (69% of cases in 2015), bacterial vaginosis (50%), chlamydia (16%), and trichomoniasis (13%); for urethral discharge were gonorrhoea (77%) and chlamydia (22%); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48%) and syphilis (9%). Distributions of infectious aetiologies were similar across regions and population subgroups but changed over time. What do these findings mean?: The findings support the applicability and continued use of World Health Organization guidelines for symptomatic STI management across SSA settings. National STI programmes should re-assess aetiologies regularly due to changes over time. Limitations of the review include that no data were available in 16 of 48 SSA countries, there was large variability in results across studies identified in the review, and certain information of interest was missing or inconsistently reported across studies. [ABSTRACT FROM AUTHOR]

Genital herpes is caused by infection with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and currently has no cure. The disease is the second-most common sexually transmitted infection in the United States, with an estimated 18.6 million prevalent genital infections caused by HSV-2 alone. Genital herpes diagnostics and treatments are not optimal, and no vaccine is currently available. The Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "CDC/NIAID Joint Workshop on Genital Herpes." This report summarizes 8 sessions on the epidemiology of genital herpes, neonatal HSV, HSV diagnostics, vaccines, treatments, cures, prevention, and patient advocacy perspective intended to identify opportunities in herpes research and foster the development of strategies to diagnose, treat, cure, and prevent genital herpes. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-related infections with the human herpes simplex virus (HSV) strains HSV-1 and HSV-2 are particularly noteworthy. There are numerous reported examples of intrapartum transmission of herpes infection, notwithstanding the extreme rarity of intrauterine transfer from mother to fetus. The purpose of this study was to evaluate the seroprevalence of HSV-1 and HSV-2 antibodies in pregnant women in the western region of Romania. Methods: Pregnant women who presented for routine pregnancy monitoring at Romania's County Clinical Emergency Hospital in Craiova between 2013 and 2016 and 2019 and 2022 were included in the study. In order to find anti-HSV-1/2 IgG antibodies, we conducted serological testing on the patients and gathered demographic information from them. Results: HSV-1 seroprevalence was shown to have declined in rural areas and increased in urban areas, with values between 2013 and 2016 being 89.30% and those between 2019 and 2022 being 84.96%, respectively. Women over 35 who were pregnant had the highest seroprevalence. The seroprevalence of HSV-2 decreased from 16.16% in 2013–2016 to 12.43% in 2019–2022, and both rural and urban areas continued to experience this declining trend. Similarly, pregnant women over 35 years old had the highest frequency of HSV-1 infections. Conclusions: Establishing educational programs and other actions to reduce the transmission rate and ultimately the prevalence of the disease can be made easier with knowledge about the seroprevalence of HSV-1 and HSV-2 infections. [ABSTRACT FROM AUTHOR]

Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a promising nucleic acid-based gene targeting approach for gene expression knock-down and modulation. The RNase P-EGS strategy is unique as an EGS can be designed to basepair any mRNA sequence and recruit intracellular RNase P for hydrolysis of the target mRNA. In this study, we provide the first direct evidence that the RNase P-based approach effectively blocks the gene expression and replication of herpes simplex virus 2 (HSV-2), the causative agent of genital herpes. We constructed EGSs to target the mRNA encoding HSV-2 single-stranded DNA binding protein ICP8, which is essential for viral DNA genome replication and growth. In HSV-2 infected cells expressing a functional EGS, ICP8 levels were reduced by 85%, and viral growth decreased by 3000 folds. On the contrary, ICP8 expression and viral growth exhibited no substantial differences between cells expressing no EGS and those expressing a disabled EGS with mutations precluding RNase P recognition. The anti-ICP8 EGS is specific in targeting ICP8 because it only affects ICP8 expression but does not affect the expression of the other viral immediate-early and early genes examined. This study shows the effective and specific anti-HSV-2 activity of the RNase P-EGS approach and demonstrates the potential of EGS RNAs for anti-HSV-2 applications. [ABSTRACT FROM AUTHOR]

Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 μg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 μg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2. [ABSTRACT FROM AUTHOR]

Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes an asymptomatic latent infection of sensory neurons of dorsal root ganglia (DRG). Chemical and physical stress cause intermittent virus reactivation from latently infected DRG and recurrent virus shedding in the genital mucosal epithelium causing genital herpes in symptomatic patients. While T cells appear to play a role in controlling virus reactivation from DRG and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T cells into DRG and the vaginal mucosa (VM) remain to be fully elucidated. The present study investigates the effect of CXCL9, CXCL10, and CXCL11 T-cell-attracting chemokines on the frequency and function of DRG- and VM-resident CD4+ and CD8+ T cells and its effect on the frequency and severity of recurrent genital herpes in the recurrent herpes guinea pig model. HSV-2 latent-infected guinea pigs were immunized intramuscularly with the HSV-2 ribonucleotide reductase 2 (RR2) protein (Prime) and subsequently treated intravaginally with the neurotropic adeno-associated virus type 8 expressing CXCL9, CXCL10, or CXCL11 chemokines to recruit CD4+ and CD8+ T cells into the infected DRG and VM (Pull). Compared to the RR2 therapeutic vaccine alone, the RR2/CXCL11 prime/pull therapeutic vaccine significantly increased the frequencies of functional tissue-resident and effector memory CD4+ and CD8+ T cells in both DRG and VM tissues. This was associated with less virus in the healed genital mucosal epithelium and reduced frequency and severity of recurrent genital herpes. These findings confirm the role of local DRG- and VM-resident CD4+ and CD8+ T cells in reducing virus shedding at the vaginal site of infection and the severity of recurrent genital herpes and propose the novel prime-pull vaccine strategy to protect against recurrent genital herpes. [ABSTRACT FROM AUTHOR]

The article focuses on the challenges and logistics of maintaining the cold chain for vaccines and other therapeutics, particularly in light of events like the COVID-19 pandemic. It explores the complexities of ensuring that these products remain at the required temperatures throughout their lifecycle, from formulation to distribution, and discusses various research avenues and innovations aimed at overcoming these challenges.

Several antiviral agents lost their efficacy due to their severe side effects and virus mutations. This study aimed to identify and optimize the conditions for exopolysaccharide (EPS) production from a newly isolated cyanobacterium, Acaryochloris Al-Azhar MNE ON864448.1, besides exploring its antiviral activity. The cyanobacterial EPS was purified through DEAE-52 cellulose column with a final yield of 83.75%. Different analysis instruments were applied for EPS identification, including Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), and gas chromatographic-mass spectrometry (GC–MS). Plackett–Burman's design demonstrated that working volume (X1), EDTA (X2), inoculum size (X3), CaCl2 (X4), and NaCl (X5) are the most important variables influencing EPS production. Central composite design (CCD) exhibited maximum EPS yield (9.27 mg/mL) at a working volume of 300 mL in a 1 L volumetric flask, EDTA 0.002 g/L, inoculum size 7%, CaCl2 0.046 g/L, and NaCl 20 g/L were applied. EPS showed potent antiviral activities at different stages of herpes simplex virus type-1 and 2 (HSV-1, HSV-2), adenovirus (ADV) and coxsackievirus (A16) infections. The highest half-maximal inhibitory concentration (IC50) (6.477 µg/mL) was recorded during HSV-1 internalization mechanism, while the lowest IC50 (0.005669 µg/mL) was recorded during coxsackievirus neutralization mechanism. [ABSTRACT FROM AUTHOR]

Background: Herpes Simplex Virus Type 2 (HSV-2) is a prevalent sexually transmitted infection with varying clinical manifestations. Understanding the longitudinal outcomes is crucial for managing and mitigating its impact on individuals and public health. Material and Methods: In this cohort study, 100 participants from the general population were assessed over a defined follow-up period to determine the prevalence, symptomatic status, outbreak frequency, quality of life impact, treatment adherence, and transmission risks. Participants underwent serological testing and completed questionnaires regarding their symptoms, antiviral therapy, and quality of life. Results: Among the 100 participants, 32 tested positive for HSV-2, resulting in a prevalence rate of 32%. Of these, 22 (70%) were symptomatic, while 10 (30%) were asymptomatic. Symptomatic individuals experienced varying outbreak frequencies, with 31% suffering from 4-6 outbreaks annually. Quality of life was significantly impacted in symptomatic individuals across social (64%), psychological (68%), physical (42%), and financial (35%) domains. In the symptomatic group, 75% were on antiviral therapy, which effectively reduced outbreak frequency and severity. Viral shedding was detected in 31% of asymptomatic individuals, while 16% of asymptomatic individuals progressed to symptomatic during follow-up. Two partner transmission cases were recorded. Conclusion: The longitudinal outcomes of HSV-2 infection highlight the varied clinical course and significant psychosocial impact, underscoring the importance of consistent monitoring, individualized management, and effective educational programs to reduce transmission risk and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Shortly after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cases of viral, bacterial, and fungal coinfections in hospitalized patients became evident. This retrospective study investigates the prevalence of multiple pathogen co-detections in 1472 lower respiratory tract (LRT) samples from 229 SARS-CoV-2-positive patients treated in the largest intensive care unit (ICU) in Slovenia. In addition to SARS-CoV-2, (rt)RT-PCR tests were used to detect cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV), and atypical bacteria: Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila/spp. At least one co-detection was observed in 89.1% of patients. EBV, HSV-1, and CMV were the most common, with 74.7%, 58.1%, and 38.0% of positive patients, respectively. The median detection time of EBV, HSV-1, and CMV after initial SARS-CoV-2 confirmation was 11 to 20 days. Bronchoalveolar lavage (BAL) and tracheal aspirate (TA) samples showed equivalent performance for the detection of EBV, CMV, and HSV-1 in patients with both available samples. Our results indicate that SARS-CoV-2 infection could be a risk factor for latent herpesvirus reactivation, especially HSV-1, EBV, and CMV. However, additional studies are needed to elucidate the clinical importance of these findings. [ABSTRACT FROM AUTHOR]