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• Testing using saliva real-time PCR on Guthrie paper for congenital CMV diagnosis. • Displays high sensitivity and specificity, rendering it a powerful screening test. • This accurate, method is a good candidate for cCMV universal screening programs. In recent years, interest in universal newborn screening for congenital cytomegalovirus (cCMV) has intensified. consequently, reliable and simple methods of mass screening for cCMV, are essential. Herein, we present a novel approach of using polymerase chain reaction (PCR) in saliva with direct inoculation onto Guthrie paper. Our aim was to determine the diagnostic accuracy of real- time PCR in saliva rolled directly onto Guthrie paper in diagnosing cCMV infection. To evaluate the diagnostic accuracy of real-time PCR analysis of dried saliva on Guthrie paper as a future approach for mass screening of newborns in diagnosing cCMV infection. This prospective, blinded study was performed in a tertiary cytomegalovirus (CMV) clinic from May 2018 through January 2019. Forty-two cCMV positive newborns and 41 without cCMV, were enrolled and tested for CMV using PCR from their saliva placed onto Guthrie paper and from their saliva using standard methods. Specificity and sensitivity of dried saliva PCR versus gold-standard methods were analyzed. Forty-two out of 42 (100 %) CMV positive infants showed positive PCR in the dried saliva on the Guthrie paper. All (100 %) controls exhibited negative PCR results. Congenital CMV infection was identified with a sensitivity of 100 % (95 % C.I. = 91.4%–100.00%) and specificity of 100 % (95 % C.I. = 91.4%–100.00%). CMV testing with saliva real-time PCR on Guthrie paper displayed a high sensitivity and specificity, rendering it a powerful screening test. The accuracy, simplicity of sampling, storage and transportation and the potential reliance on existing logistic resources, establishes this method as a candidate for cCMV universal screening programs. [ABSTRACT FROM AUTHOR]

Introduction and Objective. Guillain-Barré syndrome (GBS) is a complex clinical entity with an autoimmune basis. It is considered the most common cause of acute neuromuscular paralysis in children. The incidence of GBS is approximately 0.34 per 100 000 cases annually, with a higher prevalence in the male population. The cause of the incidence is considered to be a complication of infection or vaccination. Review Methods. The studies cited in the presented review were selected from PUBMED. The key words used for the search included: 'Guillain-Barré syndrom', 'Guillain-Barré treatment', and 'Guillain-Barré therapeutic methods'. Articles not written in English, conference abstracts only and duplicated papers were excluded. Brief description of the state of knowledge. In the 19th century, abnormalities in albimuno-cytological dissection were considered to be the cause, but today diagnostic criteria have evolved. The most important element in the diagnosis of patients is the analysis of cerebrospinal fluid and nerve conduction studies. Possible pathogens that may cause symptoms of the disease include viruses such as Epstein-Barr virus, varicella, cytomegalovirus, and SARS-CoV-2. GBS manifests itself with numerous neurological and cardiovascular symptoms, including bilateral limb weakness, facial paralysis or cardiac arrhythmias. Patient treatment includes immunotherapy immediately after diagnosis. Summary. GBS is a rapidly progressive and difficult to treat clinical entity. It is important to make a timely diagnosis and immediately implement therapy to reduce the risk of death. Further clinical research is needed to find new therapeutic options for young patients. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative. [ABSTRACT FROM AUTHOR]

Background: Seroprevalence of Cytomegalovirus infection varies between 40% and 100% worldwide. Different studies carried out in Iran indicate this variation in this country. It is important to estimate the total infection prevalence using a reliable method such as meta- analysis in order to be applied by policymakers. This study aims to estimate the IgG and IgM seroprevalences of CMV infection among Iranian women and neonates. Method: We selected eligible articles for final meta- analysis by searching the national and international databases, excluding duplicates and irrelevant papers from primarily identified studies after abstract/full text review, implementing exclusion/inclusion criteria and quality assessment. Standard error of the prevalence was calculated according to binomial distribution formula. Based on the degree of heterogeneity, fixed or random effects models were applied for estimating the pooled prevalences. Results: In this study, 16 papers providing 20 evidences of CMV prevalence in Iran entered in the meta-analysis. CMV IgG and IgM seroprevalences as well as primary infection rate (95% confidence interval) among pregnant women were 92.8% (90.6 - 94.9), 6.4% (2.8 - 9.9) and 1.1% (0.7 - 1.5) respectively. CMV IgM seroprevalence among neonates were 0.6% (0.09 - 1.2), while CMV IgG and CMV IgM seroprevalences among non-pregnant women were 78.4% (70 - 86.8) and 4.6% (1.5 - 7.6) respectively. Conclusions: This meta- analysis showed that the prevalence of CMV infection among studied population is relatively high. Therefore, mortality, complications, anomalies and injuriesamongfetuses, neonates and immunocompromized patients can be partially related to the CMV infection. [ABSTRACT FROM AUTHOR]

Currently, the diagnosis of congenital cytomegalovirus (cCMV) infection in most highly resourced countries is based on clinical suspicion alone. This means only a small proportion of cCMV infections are diagnosed. Identification, through either universal or targeted screening of asymptomatic newborns with cCMV, who would previously have gone undiagnosed, would allow for potential early treatment with antiviral therapy, ongoing audiological surveillance and early intervention if sensorineural hearing loss (SNHL) is identified. This paper systematically reviews published papers examining the potential benefits of targeted and universal screening for newborn infants with cCMV. We found that the treatment of these infants with antiviral therapy remains controversial, and clinical trials are currently underway to provide further answers. The potential benefit of earlier identification and intervention (eg, amplification and speech therapy) of children at risk of later-onset SNHL identified through universal screening is, however, clearer. [ABSTRACT FROM AUTHOR]

This paper aimed to evaluate whether human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) could shift the balance between regulatory T (Treg) and T-helper type 17 (Th17) cells in vitro. In this study, primary EVT isolated from first trimester placental tissues were infected with HCMV, and conditional media were harvested after cultivation for 72 h. T lymphocytes were cultured in the presence or absence of HCMV-infected conditional media. The frequencies of Th17 or Treg cells from HCMV group were significantly lower or higher than those from the control group, with the expression of corresponding key cytokines at both messenger ribonucleic acid and secretion levels, respectively. The ratio of Treg to Th17 cells was significantly lower in HCMV group than that in control group (P < 0.01). In conclusion, tiled Th17/Treg balance at maternal–fetal interface exists after HCMV infection. [ABSTRACT FROM AUTHOR]

Background Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances. Sources of data Sources of data are recently published research papers and reviews about HCMV treatments. Areas of agreement Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA. Areas of controversy Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection? Growing points Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells. Areas timely for developing research We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine. [ABSTRACT FROM AUTHOR]

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Agnieszka Bauer and Julia Cecilia Madela are first authors on 'Rat cytomegalovirus-encoded -chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells', published in JCS. Agnieszka is a postdoc, and Julia a Research Associate in the lab of Sebastian Voigt at Robert Koch Institute, Berlin, Germany, where they investigate host-pathogen interaction and viral immune evasion. [ABSTRACT FROM AUTHOR]

Introduction Venous thromboembolic events (VTE) occur in more than 5% of hospitalized patients with acute CMV infection. In immunocompetent patients, splanchnic vein thrombosis (SVT) and splenic infarction have been suggested to represent approximately half of the published cases of CMV-associated VTE. We performed a systematic review of the literature with the aim to describe epidemiology, clinical characteristics, treatment, and natural history of CMV-associated SVT in immunocompetent patients. Methods Studies were identified by a PubMed and Google Scholar electronic database search until January 2018. All published papers describing immunocompetent adults with SVT occurring concomitantly to an acute CMV infection were included. Results Forty-four patients with CMV-associated SVT were described in 38 papers. Twenty-three patients were male, mean age was 38.1 years (range, 17–68). Symptomatic SVT occurred in 31 patients, incidental SVT in 13 patients. In symptomatic SVT, an acute and severe onset with small bowel or splenic infarction required surgical treatment for resolution in 22.6% of cases. Anticoagulation induced both a favourable clinical outcome and a recanalization of SVT in more than 70% of the remaining cases. In incidental SVT, a favourable clinical outcome and a complete recanalization of SVT by anticoagulation were reported in more than 80% of cases. No patient with CMV-associated SVT died and no SVT recurrence was reported. Conclusions CMV-associated SVT has probably a favourable clinical course in most patients. Only future, well-designed, prospective studies with an adequate follow-up will allow to confirm the data of published cases. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin–eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection. [ABSTRACT FROM AUTHOR]

Background: Insect cell lines play a vital role in many aspects of research on disease vectors and agricultural pests. The tsetse fly Glossina morsitans morsitans is an important vector of salivarian trypanosomes in sub-Saharan Africa and, as such, is a major constraint on human health and agricultural development in the region. Methods: Here, we report establishment and partial characterisation of a cell line, GMA/LULS61, derived from tissues of adult female G. m. morsitans. GMA/LULS61 cells, grown at 28 °C in L-15 (Leibovitz) medium supplemented with foetal bovine serum and tryptose phosphate broth, have been taken through 23 passages to date and can be split 1:1 at 2-week intervals. Karyotyping at passage 17 revealed a predominantly haploid chromosome complement. Species origin and absence of contaminating bacteria were confirmed by PCR amplification and sequencing of fragments of the COI gene and pan-bacterial 16S rRNA gene respectively. However, PCR screening of RNA extracted from GMA/LULS61 cells confirmed presence of the recently described Glossina morsitans morsitans iflavirus and Glossina morsitans morsitans negevirus, but absence of Glossina pallipides salivary gland hypertrophy virus. GMA/LULS61 cells supported infection and growth of 6/7 different insect-derived strains of the intracellular bacterial symbiont Wolbachia. Conclusions: The GMA/LULS61 cell line has potential for application in a variety of studies investigating the biology of G. m. morsitans and its associated pathogenic and symbiotic microorganisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains an effective treatment modality in many hematological malignancies. Few studies directly compare rabbit anti-thymocyte globulin (r-ATG) formulations Thymoglobuline (ATG-T) and Grafalon (ATG-G). Our retrospective analysis compared the outcomes in 87 adult allo-HCT patients receiving ATG-T or ATG-G. No significant differences were found in acute graft-versus-host disease (aGvHD) incidence. However, chronic GvHD (cGvHD) was less common with ATG-T (7.5% vs. 38.3%, p = 0.001). ATG-T patients had higher cytomegalovirus (CMV) reactivation rates (70% vs. 31.9%, p < 0.001) and a shorter time to CMV (<61 days, 77.8% vs. 33.3%, p = 0.008), but were mostly asymptomatic (85.7% vs. 43.8%, p = 0.005). Overall survival (OS) and relapse-free survival (RFS) at 5 and 3 years, respectively, showed no significant differences between ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544). Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). [ABSTRACT FROM AUTHOR]

Cavitary lung lesions are uncommon radiological findings in cytomegalovirus pneumonia, and tissue biopsy is rarely performed for diagnosis. A 67‐year‐old man presented with a wet cough. Extensive white moss in the oral cavity was found on physical examination, and chest computed tomography revealed an approximately 4 cm cavitary lesion in the upper lobe of the right lung. Blood tests showed a critically low CD4+ T lymphocyte count and positivity for human immunodeficiency virus type 1 antibodies. A transbronchial biopsy of the cavitary lung lesion was performed, and inclusion bodies in the nuclei of enlarged alveolar epithelial cells were seen in the histopathological findings. Immunohistochemistry staining for cytomegalovirus was positive, and cytomegalovirus pneumonia was diagnosed. Ganciclovir treatment was initiated, and the symptoms and imaging findings resolved. Cytomegalovirus pneumonia can present as cavitary lung lesions in patients with acquired immunodeficiency syndrome, and a transbronchial biopsy is essentially useful for a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein–Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU–BSI), ventilator-associated pneumonia (VAP). Design: Observational retrospective cohort study. Setting: COVID-19 Intensive Care Unit. Patients: From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU–BSI was evaluated according to clinical judgement and specific diagnostic criteria. Measurements and main results: One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02–5.89), ICU–BSI (OR = 2.37, 95% CI 1.06–5.29) and VAP (OR = 2.64, 95% CI 1.20–5.82). Conclusions: Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU–BSI. Key points: Question: The impact of Human Herpesviruses reactivations on the morbidity and mortality of COVID-19 critically ill patients is controversial. Findings: Critically ill patients with COVID-19 are at high risk for both EBV, HSV and CMV reactivations. Meanings: Further large prospective studies will be necessary to clarify if the presence of active viral replication must be considered causal agent affecting mortality or the indirect manifestation of immune paralysis in the worst patients. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction. Case presentation: A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. Conclusions: The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus. [ABSTRACT FROM AUTHOR]

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00417-020-05038-3 [ABSTRACT FROM AUTHOR]

Recurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation. Here, we studied the consequences of the arms race between US11 and primate MHC-A proteins, leading us to uncover a tit-for-tat coevolution and its impact on MHC-A diversification. We found that US11 spurred MHC-A adaptation to evade viral antagonism: In an ancestor of great apes, the MHC-A A2 lineage acquired a Pro184Ala mutation, which confers resistance against the ancestral US11 targeting strategy. In response, US11 deployed a unique low-complexity region (LCR), which exploits the MHC-I peptide loading complex to target the MHC-A2 peptide-binding groove. In addition, the global spread of the human HLA-A*02 allelic family prompted US11 to employ a superior LCR strategy with an optimally fitting peptide mimetic that specifically antagonizes HLA-A*02. Thus, despite cytomegaloviruses low pathogenic potential, the increasing commitment of US11 to MHC-A has significantly promoted diversification of MHC-A in hominids. [ABSTRACT FROM AUTHOR]

This document is a corrigendum for an article on the treatment patterns of antiviral prophylaxis for cytomegalovirus (CMV) among adult kidney transplant recipients. The corrigendum acknowledges mistakes in the original article and provides corrected versions of the affected elements. The text provides information on the duration of CMV prophylaxis in kidney transplant recipients based on their risk group. Factors such as geographic location, comorbidities, and wait time were associated with a higher likelihood of discontinuing CMV prophylaxis. The document also includes baseline demographic, clinical, and medication-related characteristics of adult kidney transplant recipients. [Extracted from the article]

Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female rabbits with monovalent (gB-1), bivalent (gB-1+gB-3), or pentavalent (gB-1+gB-2+gB-3+gB-4+gB-5) gB lipid nanoparticle-encapsulated nucleoside-modified RNA (mRNA–LNP) vaccines. The multivalent vaccine groups did not demonstrate a higher magnitude or breadth of the IgG response to the gB ectodomain or cell-associated gB compared to that of the monovalent vaccine. Also, the multivalent vaccines did not show an increase in the breadth of neutralization activity and antibody-dependent cellular phagocytosis against HCMV strains encoding distinct gB genotypes. Interestingly, peripheral blood mononuclear cell-derived gB-2-specific T-cell responses elicited by multivalent vaccines were of a higher magnitude compared to that of monovalent vaccinated animals against a vaccine-mismatched gB genotype at peak immunogenicity. Yet, no statistical differences were observed in T cell response against gB-3 and gB-5 variable regions among the three vaccine groups. Our data suggests that the inclusion of multivalent gB antigens is not an effective strategy to increase the breadth of anti-HCMV gB antibody and T cell responses. Understanding how to increase the HCMV vaccine protection breadth will be essential to improve the vaccine efficacy. [ABSTRACT FROM AUTHOR]

In response to viral infection, cells can initiate programmed cell death (PCD), leading to a reduction in the release of viral progeny. Viruses have therefore evolved specific mechanisms to curb PCD. Cytomegaloviruses (CMVs) are sophisticated manipulators of cellular defenses and encode potent inhibitors of apoptosis and necroptosis. However, a CMV inhibitor of pyroptosis has not been clearly identified and characterized. Here we identify the mouse cytomegalovirus M84 protein as an inhibitor of pyroptosis and proinflammatory cytokine release. M84 interacts with the pyrin domain of AIM2 and ASC to inhibit inflammasome assembly. It thereby prevents Caspase-1-mediated activation of interleukin 1β (IL-1β), IL-18, and Gasdermin D. Growth attenuation of an M84-deficient MCMV in macrophages is rescued by knockout of either Aim2 or Asc or by treatment with a Caspase-1 inhibitor, and its attenuation in infected mice is partially rescued in Asc knockout mice. Thus, viral inhibition of the inflammasome-pyroptosis pathway is important to promote viral replication in vivo. Viruses have evolved specific mechanisms to reduce programmed cell death in order to prolong survival. Here the authors show a mouse cytomegalovirus (MCMV) encoded protein that inhibits pyroptosis, proinflammatory cytokine release and the assembly of inflammasomes. [ABSTRACT FROM AUTHOR]

Conventional antiviral memory CD4 T cells typically arise during the first two weeks of acute infection. Unlike most viruses, cytomegalovirus (CMV) exhibits an extended persistent replication phase followed by lifelong latency accompanied with some gene expression. We show that during mouse CMV (MCMV) infection, CD4 T cells recognizing an epitope derived from the viral M09 protein only develop after conventional memory T cells have already peaked and contracted. Ablating these CD4 T cells by mutating the M09 genomic epitope in the MCMV Smith strain, or inducing them by introducing the epitope into the K181 strain, resulted in delayed or enhanced control of viral persistence, respectively. These cells were shown to be unique compared to their conventional memory counterparts; producing higher IFNγ and IL-2 and lower IL-10 levels. RNAseq analyses revealed them to express distinct subsets of effector genes as compared to classical CD4 T cells. Additionally, when M09 cells were induced by epitope vaccination they significantly enhanced protection when compared to conventional CD4 T cells alone. These data show that late-rising CD4 T cells are a unique memory subset with excellent protective capacities that display a development program strongly differing from the majority of memory T cells. Author summary: Functional memory T cells are critical to ultimately control chronic viral infection. We show that cytomegalovirus (CMV) induces a population of unique memory CD4 T cells that expand late during infection and resolve viral persistence much better than conventional T memory cells. Mutation of the genomic CMV epitope recognized by these T cells results in markedly enhanced persistent replication, and introduction of the epitope into a CMV strain that lacks it induces much quicker resolution of persistence. When induced via vaccination, we show these T cells provide significantly enhanced protection against acute viral challenge. Together our study identifies a novel population of CD4 T cells that utilize distinct effector function(s) to rapidly resolve persistent viral replication. [ABSTRACT FROM AUTHOR]

Objectives: Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. Methods: We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. Results: The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. Conclusions: PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised. [ABSTRACT FROM AUTHOR]

Background: Both humoral and cell-mediated immunity of the patient affected by multiple myeloma (MM) are impaired; thus, infection is the main cause of the onset of symptoms and death caused by MM. Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barre syndrome (GBS) is thought to be related to immune damage, and most patients have cytomegalovirus (CMV), Epstein-Barr virus (EBV), or mycoplasma infection before onset. Cases of GBS secondary to MM are rare. Methods: We provide a case of GBS caused by cytomegalovirus infection after MM treatment, and briefly review the existing literature. Results: Secondary GBS after MM. This patient received active treatment. The clinical symptoms are gradually improving. Conclusions: The use of bortezomib has the risk of reactivating the virus. It is more about the reactivation of hepatitis B virus. Nonetheless, cytomegalovirus and Epstein-Barr virus shall have our attention. Patients with MM need to monitor CMV, regularly, especially during the treatment of bortezomib. At the same time, they also need to closely monitor the symptoms and signs of the nervous system to guard against the occurrence of GBS. [ABSTRACT FROM AUTHOR]

Objective(s): Human cytomegalovirus (CMV), a double-strand DNA herpesvirus, can be transmitted via blood transfusion which is especially important for immunocompromised recipients and can cause a fatal infection. CMV seroprevalence in Iran was studied on blood donors, healthy subjects, and some patients. Highly variable rates were detected. The purpose of this study was to review CMV seroprevalence in blood donors and apparently healthy individuals, in Iran. Materials and Methods: One hundred and fifty-eight electronic and paper-based resources and databases including published articles in internal and external journals, seminars, dissertations, and theses available in the database and different websites were used to be systematically reviewed as a meta-analysis. Less related articles to the issue, papers of specific high risk population, and articles with not enough information, were excluded. Eventually 22 articles that satisfied our selection criteria were systematically reviewed and analyzed. To explore heterogeneity between studies the I square (I2) index was used. Data were analyzed using the statistical software package (STATA) 11. Results: The heterogeneity between selected studies was 97% with an I2 statistic. In this study a random effects model was used for meta-analysis. The prevalence of CMV IgG and CMV IgM antibodies in the country were estimated to be 92% (95% CI: 90-94) and 2.6% (95% CI: 1.7-3.6), respectively. Conclusion: Given high rate of CMV seropositivity in Iran, it seems that CMVAbs screening would not be a reasonable and affordable approach to prevent CMV infection via transfusion especially for immune compromised recipients, so alternative strategies should be considered. [ABSTRACT FROM AUTHOR]

Introduction: Vertical transmission of Cytomegalovirus (CMV), resulting in congenital CMV (cCMV) infection could have disabling and potentially fatal effects on the foetus or neonate. Although primary infection probably has a higher risk of leading to cCMV, in highly seropositive populations, a significant risk of vertical transmission is thought to be due to CMV reactivation and or reinfection during pregnancy. In this narrative review, we summarise the prevalence of CMV infection and associated risk factors among pregnant African women, in a setting where primary CMV infection usually occurs during infancy. Methodology: A systematic search of literature published between January 2000 and January 2019, retrieved on five bibliographic databases was performed. Search for relevant articles was performed using the following keywords: cytomegalovirus, CMV, infection, antenatal infections, pregnancy, pregnant women, gravidity, developing countries and Africa, with appropriate qualifiers such as OR, AND. Results: Systematic searching retrieved 11 relevant original research papers. Prevalence of anti-CMV IgG and IgM antibodies ranged from 60-100% and 0-15.5%, respectively. Prevalence of CMV DNA ranged from 0-29%, depending on the specimen used. However, there was no geographic trend for CMV seroprevalence or CMV DNA prevalence across the African continent. Overall, a substantial percentage of women of reproductive-age were CMV seronegative and at risk of primary infection. Associations of sociodemographic factors with CMV infection were inconsistent across all reviewed studies. Conclusions: The limited data and inconsistency of findings from the few studies carried out in Africa calls for prospective studies comparing prevalence and outcomes of cCMV in infants born to women with both primary and reactivated CMV in Africa. [ABSTRACT FROM AUTHOR]

Background: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive. [ABSTRACT FROM AUTHOR]

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59. We characterize gB-specific monoclonal antibodies isolated from individuals vaccinated with a disabled infectious single cycle (DISC) CMV vaccine, V160, and compare these to the gB-specific monoclonal antibody repertoire isolated from naturally-infected individuals. We find that vaccination with V160 resulted in gB-specific antibodies that bound homogenously to gB expressed on the surface of a cell in contrast to antibodies isolated from natural infection which variably bound to cell-associated gB. Vaccination resulted in a similar breadth of gB-specific antibodies, with binding profile to gB genotypes 1–5 comparable to that of natural infection. Few gB-specific neutralizing antibodies were isolated from V160 vaccinees and fewer antibodies had identifiable gB antigenic domain specificity compared to that of naturally-infected individuals. We also show that glycosylation of gB residue N73 may shield binding of gB-specific antibodies. [ABSTRACT FROM AUTHOR]

COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. CAPA occurred in 96 patients (16.6%) of the 579 patients analyzed. Among the CAPA population, 40 (41.7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7–27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p = 0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21–4.48, p = 0.011). In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (CMV) is a major pathogen after solid organ transplantation, leading to high morbidity and mortality. Transplantation from a CMV-seropositive donor to a CMV-seronegative recipient (D+/R−) is associated with high risk of CMV disease. However, that risk is not uniform, suggesting a role for host factors in immune control of CMV. To identify host genetic factors that control CMV DNAemia post transplantation, we performed a whole-exome association study in two cohorts of D+/R− kidney transplant recipients. Quantitative CMV DNA was measured for at least one year following transplantation. Several CMV-protective single-nucleotide polymorphisms (SNPs) were identified in the first cohort (72 patients) but were not reproducible in the second cohort (126 patients). A meta-analysis of both cohorts revealed several SNPs that were significantly associated with protection from CMV DNAemia. The copy number variation of several genes was significantly different between recipients with and without CMV DNAemia. Amongst patients with CMV DNAemia in the second cohort, several variants of interest (p < 5 × 10−5), the most common of which was NLRC5, were associated with peak viral load. We provide new predictive genetic markers for protection of CMV DNAemia. These markers should be validated in larger cohorts. [ABSTRACT FROM AUTHOR]

Temperature is a well-known effector of several transmission factors of mosquito-borne viruses, including within mosquito dynamics. These dynamics are often characterized by vector competence and the extrinsic incubation period (EIP). Vector competence is the intrinsic ability of a mosquito population to become infected with and transmit a virus, while EIP is the time it takes for the virus to reach the salivary glands and be expectorated following an infectious bloodmeal. Temperatures outside the optimal range act on life traits, decreasing transmission potential, while increasing temperature within the optimal range correlates to increasing vector competence and a decreased EIP. These relatively well-studied effects of other Aedes borne viruses (dengue and Zika) are used to make predictions about transmission efficiency, including the challenges presented by urban heat islands and climate change. However, the knowledge of temperature and chikungunya (CHIKV) dynamics within its two primary vectors—Ae. aegypti and Ae. albopictus—remains less characterized, even though CHIKV remains a virus of public-health importance. Here, we review the literature and summarize the state of the literature on CHIKV and temperature dependence of vector competence and EIP and use these data to demonstrate how the remaining knowledge gap might confound the ability to adequately predict and, thus, prepare for future outbreaks. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is a highly prevalent opportunistic infection among liver transplant recipients. When the liver donor is infected with CMV, there is a risk of transmission to the recipient, leading to CMV infection. To improve the postoperative outcome of liver transplantation, it is crucial to shift the focus of CMV detection to the donor and achieve early diagnosis, as well as implement effective preventative and therapeutic measures. However, the commonly used CMV detection methods in the past had limitations that prevented their early and accurate diagnosis in liver transplant donors. This review focuses on the latest advancements in CMV detection methods that can potentially be applied to liver transplant donors. The objective is to compare and evaluate their clinical utility, thereby providing guidance and support for rapid and accurate diagnosis of CMV infection in the clinic. The clustered regularly interspaced short palindromic repeats-associated proteins (CRISPR–Cas) system-based assay emerges as a promising method for detecting the virus, offering great prospects for early and expedient CMV infection diagnosis in clinical settings. [ABSTRACT FROM AUTHOR]

Human Cytomegalovirus (HCMV) is a ubiquitous member of the Herpesviridae family, responsible for the most common congenital viral infection—congenital Cytomegalovirus (cCMV) infection. While a majority of HCMV infections in children and adults are asymptomatic, HCMV is well known to cause severe infections in the immunocompromised individual and maternal infections with variable long-term sequelae after maternal–fetal transmission with primary or nonprimary infections. HCMV seroprevalence and cCMV incidence vary by geographic area and demographic characteristics like race and socioeconomic status. While cCMV birth prevalence ranges from 0.2% to 6% in different parts of the world, it is influenced by regional HCMV seroprevalence rates. HCMV screening during pregnancy is not routinely offered due to lack of awareness, hurdles to accurate diagnosis, and lack of well-established effective treatment options during pregnancy. This review will focus on antiviral treatment options currently available for use during pregnancy and in the newborn period for the treatment of maternal and congenital HCMV infections. [ABSTRACT FROM AUTHOR]

Approximately 0.7% of infants are born with congenital cytomegalovirus (CMV), making it the most common congenital infection. About 1 in 5 congenitally infected babies will suffer long-term sequelae, including sensorineural deafness, intellectual disability, and epilepsy. CMV infection is highly species-dependent, and the rhesus CMV (RhCMV) infection of rhesus monkey fetuses is the only animal model that replicates essential features of congenital CMV (cCMV) infection in humans, including placental transmission, fetal disease, and fetal loss. Using experimental data from RhCMV seronegative rhesus macaques inoculated with RhCMV in the late first to early second trimesters of pregnancy, we built and calibrated a mathematical model for the placental transmission of CMV. The model was then used to study the effect of the timing of inoculation, maternal immune suppression, and hyper-immune globulin infusion on the risk of placental transmission in the context of primary and reactivated chronic maternal CMV infection. [ABSTRACT FROM AUTHOR]

The successful implementation of area-wide integrated tsetse control using the Sterile Insect Technique (SIT) relies on various factors. These include adapting and mass-producing the wild strain in the laboratory, suppressing the wild population in the target area, and releasing competent sterile male flies into the targeted area. Two important factors that can influence the effectiveness of this strategy are the presence of tsetse endosymbionts, specifically Sodalis glossinidius, and the infection of salivary gland hypertrophy virus (SGHV). SGHV infection directly hampers the expansion of Glossina pallidipes colonies in mass-rearing facilities by negatively impacting reproduction (fertility and fecundity), and overall growth. The viral infections in other tsetse species indirectly affect G. pallidipes by serving as a source of infection, as these species are less susceptible to clinical manifestations of the virus. The role of S. glossinidius in this context remains inconclusive despite previous laboratory and field studies, highlighting the need for further research. In addition to knowledge generation, it is crucial to introduce healthy fly populations from the wild into the insectary for sustainable mass-rearing production. In this study, our objective was to determine the prevalence of Sodalis, SGHV, and trypanosome infections in wild populations of tsetse fly G. pallidipes and investigate potential interactions among them. We analyzed 146 dissected midgut and mouthparts samples from non-teneral flies collected from the Makao Wildlife Management Area (WMA) interface. Our results revealed a prevalence of trypanosome infection at 12.3%, SGHV infection at 7.5%, and Sodalis at 51.4%. Co- existence of SGHV infection and Sodalis was observed in 9.6% of the flies. We did not find a statistically significant association of trypanosome infections occurrence with either SGHV infection or Sodalis. However, a significant association with trypanosome infection was observed when the both Sodalis and SGHV infection co-existed in the tsetse flies. Furthermore, we identified a negative correlation between Sodalis and SGHV infections. In conclusion, our study highlights the association between the co- existence of Sodalis and SGHV and the prevalence of trypanosome infections in wild populations of G. pallidipes. These findings contribute to our understanding of the interactions among these microbes, which is crucial for the development and implementation of effective tsetse control strategies using the Sterile Insect Technique (SIT). [ABSTRACT FROM AUTHOR]

Background and Aim: Blueberries, scientifically known as Vaccinium corymbosum L., contain various secondary metabolites such as flavonoids and phenolic acids. These compounds are recognized for their potential in preventing cancer and antimicrobial properties. Materials and Methods: The extract's antibacterial activity was assessed using the time-killing assay, while its anticancer activity was evaluated using the MTT assay. Results and Conclusion: The findings from the antibacterial tests revealed that the fruit extracts exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at concentrations of 3.5-4.2 mg/mL and 5.6- 5.9 mg/mL, respectively. Furthermore, the MTT assay demonstrated that the blueberry extract displayed cytotoxic effects on cancer cell lines (HeLa and MCF7), while it showed no significant cytotoxicity on normal cells (L929). Treatment with the unripe blueberry fruit extract significantly decreased the viability of cancer cells compared to the other extracts. Specifically, the highest level of cellular toxicity among all extracts was observed in the HeLa cancer cell line at a concentration of 1.5 mg/L after 72 hours (more than 90%). Based on these findings, it can be concluded that blueberry fruit extract possesses enhanced antibacterial and anticancer properties. Moreover, this study indicated that the early stages of fruit growth exhibit greater cytotoxic effects against cancer and bacterial cells. These results significantly affect the food, pharmaceutical, and plant biotechnology industries. [ABSTRACT FROM AUTHOR]

Objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients.Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis.Results: In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes.Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy. [ABSTRACT FROM AUTHOR]

Purpose: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. Methodology: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A–E viruses, cytomegalovirus, Epstein–Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. Results: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. Conclusion: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV− reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs. [ABSTRACT FROM AUTHOR]

Background Polymerase chain reaction (PCR) testing of saliva swabs has been shown to be an attractive method to screen for congenital cytomegalovirus (CMV) infection. However, few data are available regarding the impact of pre-analytic methods on CMV DNA recovery from saliva samples under various conditions. Objectives The purpose of this study was to evaluate the impact of various transport media and transport conditions on the recovery of CMV DNA from spiked and clinical saliva samples from newborns using PCR testing. Study design Negative control saliva samples were spiked with known concentrations of World Health Organization CMV standards. Collection was simulated using filter paper and different types of swabs which were stored either dry or in various transport media at specified temperatures. Specimens were tested by quantitative PCR at multiple time points. Results were compared with samples taken from newborns infected with CMV using the same methods. Results Nucleic acid stabilization media demonstrated superior CMV stability for up to 3 weeks. Also observed was a reduction in the quantity of spiked CMV DNA over time in swab samples stored at room temperature without media or in conventional universal transport media. Swab samples from newborns infected with CMV did not demonstrate loss of CMV DNA after a week of room temperature storage in nucleic acid stabilization media or conventional universal transport media. Conclusions Although nucleic acid preservation media appear to enhance CMV DNA recovery from spiked control samples over prolonged transport times and diverse conditions, this differential yield appears be to less significant for actual clinical samples collected from infected newborns. Further evaluation of pre-analytic conditions using actual clinical samples is warranted. [ABSTRACT FROM AUTHOR]

Little is published on cytomegalovirus (CMV) serological screening at the first antenatal visit or the contemporary CMV seroprevalence rates among the Australian pregnant population. We performed a retrospective analysis of public hospital births in a major tertiary centre (n = 840) over a two month period. We found that 13.6% (95% confidence interval (CI) 11.4–16.1%) of women had been screened for CMV at their first antenatal visit with their general practitioner. Of these, 43.0% (95% CI 34.3–52.1%) were CMV seronegative and therefore susceptible to primary infection. Seronegative women were also more likely to have been born in an economically developed country, to live in a socio‐economically advantaged postcode and to be nulliparous. The information from this study may help guide future studies of congenital CMV risk reduction strategies. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue‐resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) is a common viral infection in kidney transplant recipients (KTR) that has been associated with negative outcomes. The effect on outcomes of concordance versus discordance in CMV between two different recipients of kidneys from the same donor is largely unknown. Methods: We reviewed all adult deceased donor kidney transplant recipients (DDKTs) for which both kidneys were transplanted to two different recipients at our center between 2014 and 2019. Recipient pairs from each donor were divided into groups based on concordance or discordance for the development of CMV viremia between the pair; concordant no CMV (cc‐no‐CMV) if neither KTR developed CMV, concordant CMV (cc‐CMV) if both KTRs developed CMV. The discordant group was then further divided based on the individual development of CMV (dc‐CMV) or lack of development of CMV (dc‐no‐CMV). Patient mortality and death‐censored graft failure (DCGF) were outcomes of interest. Results: Of 578 KTRs, 67% were cc‐no‐CMV, 5% were cc‐CMV, 14% were dc‐no‐CMV, and 14% dc‐CMV. Some of the baseline characteristics differ among the groups including a higher prevalence of high‐risk serostatus (D+/R‐) in cc‐CMV (32%) and dc‐CMV (32%). In multivariate analysis, with reference to cc‐no‐CMV, dc‐CMV was associated with increased risk for DCGF (HR 3.13, 95% CI 1.58–6.19), and so was delayed graft function. Factors associated with increased risk of mortality were advanced recipient age and DGF. cc‐CMV was neither associated with mortality nor DCGF. Conclusions: These findings support that in certain contexts, CMV viremia has adverse allograft outcomes, and this is highlighted when illustrated via discordance in CMV between pair kidneys from the same deceased donor. [ABSTRACT FROM AUTHOR]

To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo. Fibroblasts are an established cell type permissive for cytomegalovirus infection. Here the authors identify a population of fibroblast cells that can support murine cytomegalovirus lytic and latent virus infection in vivo and propose STAT1 as critically involved in murine cytomegalovirus latency. [ABSTRACT FROM AUTHOR]

Simple Summary: House flies have been global pests of humans and animals since antiquity, and are notoriously difficult to control. Flies in nature are sometimes infected with salivary gland hypertrophy virus (MdSGHV), which prevents them from mating or laying eggs. A better understanding of how the virus works could be helpful for through use as a fly management tool. In this study, we found that infected female flies, which normally do not mate, could be induced to mate by treating them with hormones that are involved in normal fly reproduction. The results provide insight into the mechanisms by which the virus tricks the fly into being unresponsive to male suitors. Infection with salivary gland hypertrophy virus (MdSGHV) of Musca domestica prevents female flies from accepting copulation attempts by healthy or virus-infected males. This study focused on supplemental hormonal rescue therapy for mating behavior in virus-infected female house flies. The inhibitory effect of the virus on mating behavior in females injected with MdSGHV was reversed by hormonal therapy in the form of octopamine injections, topical application of methoprene, or both therapies combined along with 20-hydroxyecdysone. Infected females whose mating responsiveness had been restored continued to have other viral pathologies associated with infection such as hypertrophy of the salivary glands and a lack of ovarian development. [ABSTRACT FROM AUTHOR]