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The human herpesvirus (HHV) family is a group of enveloped DNA viruses containing 8 members known to produce oral mucosal lesions. Following initial exposure, which may result in symptomatic primary infection, the viruses establish latency within specific cells/tissues. After reactivation, herpesviruses can cause localized symptomatic or asymptomatic recurrent (secondary) infections or diseases. HHV may have a significant role in the cause of oral mucosal infectious diseases in immunocompromised patients. This article discusses the role of those herpesviruses that can induce oral mucosal lesions, with focus on the clinical features and treatment/management., Competing Interests: Disclosure, (Copyright © 2022 Elsevier Inc. All rights reserved.)

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected almost one hundred million people since the end of 2019, killed over two million, and caused worldwide social and economic disruption. Because the mechanisms of SARS-CoV-2 infection of host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy. Besides severe respiratory and systematic symptoms, several comorbidities increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we report that SARS-CoV-2 encoded proteins and some currently used anti-COVID-19 drugs are able to induce lytic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses, through manipulation of intracellular signaling pathways. Our data indicate that those KSHV + patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.

The importance of viral infections as a leading cause of morbidity and mortality is well documented in severely immunosuppressed patients undergoing allogeneic stem cell transplantation. By contrast, viral infections generally receive less attention in patients with malignant disorders undergoing chemotherapy, where the onset of neutropenic fever is mostly associated with bacterial or fungal infections, and screening for viral infections is not routinely performed. To address the occurrence of invasive viral infections in a clinical setting commonly associated with less pronounced immunosuppression, we have prospectively screened 237 febrile neutropenic episodes in pediatric (n = 77) and adult (n = 69) patients undergoing intensive chemotherapy, primarily for treatment of acute leukemia. Serial peripheral blood specimens were tested by RQ-PCR assays for the presence and quantity of the clinically relevant viruses CMV, EBV, HHV6 and HAdV, commonly reactivated in highly immunocompromised patients. Viremia was documented in 36 (15%) episodes investigated, including the detection of HHV6 (n = 14), EBV (n = 15), CMV (n = 6), or HAdV (n = 1). While low or intermediate levels of viremia (<10 4 virus copies/mL) were commonly associated with bacterial or fungal co-infection, viremia at higher levels (>10 4 copies/mL) was documented in patients without evidence for other infections, raising the possibility that at least in some instances the onset of fever may have been attributable to the virus detected. The observations suggest that viral infections, potentially resulting from reactivation, might also play a clinically relevant role in patients receiving chemotherapy for treatment of malignant neoplasms, and routine screening for viremia in this clinical setting might be warranted., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Natural killer (NK) cells are the predominant innate lymphocytes that provide early defense against infections. In the inflammatory milieu, NK cells modify their metabolism to support high energy demands required for their proliferation, activation, and functional plasticity. This metabolic reprogramming is usually accompanied by the upregulation of nutrient transporter expression on the cell surface, leading to increased nutrient uptake required for intense proliferation. The interleukin-1 family members of inflammatory cytokines are critical in activating NK cells during infection; however, their underlying mechanism in NK cell metabolism is not fully elucidated. Previously, we have shown that IL-18 upregulates the expression of solute carrier transmembrane proteins and thereby induces a robust metabolic boost in NK cells. Unexpectedly, we found that IL-18 signaling is dispensable during viral infection in vivo , while the upregulation of nutrient transporters is primarily MyD88-dependent. NK cells from Myd88 -/- mice displayed significantly reduced surface expression of nutrient receptors and mTOR activity during MCMV infection. We also identified that IL-33, another cytokine employing MyD88 signaling, induces the expression of nutrient transporters but requires a pre-exposure to IL-12. Moreover, signaling through the NK cell activating receptor, Ly49H, can also promote the expression of nutrient transporters. Collectively, our findings revealed multiple pathways that can induce the expression of nutrient transporters on NK cells while highlighting the imperative role of MyD88 in NK cell metabolism during infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khan, Almutairi, Ali, Salcedo, Stewart, Wang and Lee.)

Background: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated., Objective: To classify the most common adverse reactions associated with dupilumab treatment in patients with AD., Methods: The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group., Results: The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab., Limitations: Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated., Conclusions: Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Serious burn trauma is associated with changes of the immune system, and immunosuppression induced by burn trauma can lead to reactivation of latent infections. Herpetic viruses are known for their lifelong persistence after primary infection and ability to reactivate. Their reactivation in the setting of burn trauma or primary infection can cause serious complications for a weakened burn patient. Presented is a case of a toddler who sustained second-degree scald burns over 20% of his body surface area. The injury was complicated by a multi-resistant bacterial infection in addition to reactivation of a latent HHV-6 infection concurrently with a primary HSV-1 infection. Described further are basic diagnostics, local and systemic treatment strategies, and other complications due to disseminated herpetic infections. To date, HHV-6 reactivation has not been described in conjunction with burn injury.

Background: Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria coinfections. However, the role of Kaposi sarcoma-associated herpesvirus (KSHV), also endemic in Africa, has not been evaluated as a cofactor in eBL pathogenesis., Methods: Multiplexed seroprofiles for EBV, malaria, and KSHV were generated for 266 eBL patients, 78 non-eBL cancers, and 202 healthy children. KSHV and EBV loads were quantified by PCR., Results: KSHV seroprevalence did not differ by study group but was associated with age. Seropositivity, defined by K8.1/LANA or in combination with 5 other KSHV antigens (ORF59, ORF65, ORF61, ORF38, and K5) was associated with antimalarial antibody levels to AMA1 (odds ratio [OR], 2.41, P < .001; OR, 2.07, P < .001) and MSP1 (OR, 2.41, P = .0006; OR, 5.78, P < .001), respectively. KSHV loads did not correlate with antibody levels nor differ across groups but were significantly lower in children with detectable EBV viremia (P = .014)., Conclusions: Although KSHV-EBV dual infection does not increase eBL risk, EBV appears to suppress reactivation of KSHV while malaria exposure is associated with KSHV infection and/or reactivation. Both EBV and malaria should, therefore, be considered as potential effect modifiers for KSHV-associated cancers in sub-Saharan Africa., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Cheetahs ( Acinonyx jubatus ) are particularly susceptible to feline herpesvirus-1 (FHV-1). Recommendations for preventive health care in cheetahs include vaccination against FHV-1 using killed and modified live virus (MLV) vaccines. Although MLV vaccines tend to induce a more robust immune response than killed vaccines, they can induce disease. This case series details an FHV-1 outbreak in four adult cheetahs following the use of MLV vaccine in one of them. All four cheetahs developed severe FHV-1 clinical signs and were euthanized. Clinical signs included depression, anorexia, nasal discharge, ocular discharge, sneezing, and ulcerative dermatitis. Herpesvirus infection was diagnosed using history, clinical signs, polymerase chain reaction, and histologic evaluation. The timeline of events suggests the MLV vaccine was the inciting cause, although this was not conclusively proven. Outcome of this case suggests that when considering MLV vaccines for cheetahs, careful risk and benefit discussions are merited.

Purpose: Mycophenolate mofetil (MMF) is a steroid-sparing immunosuppressant used extensively to treat both common and rare dermatological conditions. Its lymphocyte specificity makes it a favorable therapeutic option particularly for patients who cannot tolerate alternative immunosuppressants. However, the side effect profile of MMF has not been extensively evaluated. This review presents current evidence regarding increased risk of human herpesvirus infection (HHV) with MMF therapy. Methods: The electronic database Medline (OVID) was searched on January 2018 for relevant English-language articles regarding the evaluation of incidence/prevalence of HHV infection in patients taking MMF, identifying 24 studies. Results: The majority of available studies were conducted on solid organ transplant recipients receiving complex immunosuppressive treatment including the MMF. Cytomegalovirus is the most well studied of the HHV. A positive association with cytomegaloviruses was found with MMF when compared to alternative immunosuppressants and studies to date suggest dose-dependent effect. Conclusion: MMF is a commonly used steroid-sparing agent used to treat dermatological conditions. This review highlights that MMF is positively associated with cytomegalovirus infection. The presented studies were heterogeneous in study design and detection method, with the majority completed on renal transplant patients. Further studies are needed to shed light on the association of MMF with HHV.

The increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein-Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV-6 were detected and quantified by TaqMan real-time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV-6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor-based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)-based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV-disease was correlated with MMF-based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10 4 copies/mL) was related to acute allograft rejection., (© 2019 Wiley Periodicals, Inc.)

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HHV-6A, HHV-6B, HHV-7, and HHV-8 in the pre- and post-transplant period. The majority of HHV-6 (A and B) and HHV-7 infections in transplant recipients are asymptomatic; symptomatic disease is reported infrequently across organs. Routine screening for HHV-6 and 7 DNAemia is not recommended in asymptomatic patients, nor is prophylaxis or preemptive therapy. Detection of viral nucleic acid by quantitative PCR in blood or CSF is the preferred method for diagnosis of HHV-6 and HHV-7 infection. The possibility of chromosomally integrated HHV-6 DNA should be considered in individuals with persistently high viral loads. Antiviral therapy should be initiated for HHV-6 encephalitis and should be considered for other manifestations of disease. HHV-8 causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease and is also associated with hemophagocytic syndrome and bone marrow failure. HHV-8 screening and monitoring may be indicated to prevent disease. Treatment of HHV-8 related disease centers on reduction of immunosuppression and conversion to sirolimus, while chemotherapy may be needed for unresponsive disease. The role of antiviral therapy for HHV-8 infection has not yet been defined., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This review discusses the epidemiologic and clinical aspects of herpes viruses other than cytomegalovirus in patients who have undergone hematopoietic stem cell transplantation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Kaposi's Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, which is the most common cancer in acquired immune deficiency syndrome patients. KSHV contains a variety of immunoregulatory proteins. There have been many studies on the modulation of antiviral response by these immunoregulatory proteins of KSHV. However, the antiviral effects of extracellular vesicles (EVs) during de novo KSHV infection have not been investigated to our best knowledge. In this study, we showed that KSHV-infected cells induce interferon-stimulated genes (ISGs) response but not type I interferon in uninfected bystander cells using EVs. mRNA microarray analysis showed that ISGs and IRF-activating genes were prominently activated in EVs from KSHV-infected cells (KSHV EVs)-treated human endothelial cells, which were validated by RT-qPCR and western blot analysis. We also found that this response was not associated with cell death or apoptosis by virus infection. Mechanistically, the cGAS-STING pathway was linked with these KSHV EVs-mediated ISGs expressions, and mitochondrial DNA on the surface of KSHV EVs was one of the causative factors. Besides, KSHV EVs-treated cells showed lower infectivity for KSHV and viral replication activity than mock EVs-treated cells. Our results indicate that EVs from KSHV-infected cells could be an initiating factor for the innate immune response against viral infection, which may be critical to understanding the microenvironment of virus-infected cells.

Pollens are well-known triggers of respiratory allergies and asthma. The pollen burden in today's ambient air is constantly increasing due to rising climate change and air pollution. How pollens interact with the respiratory mucosa remains largely unknown due to a lack of representative model systems. We here demonstrate how pollen proteases of Kentucky bluegrass, white birch and hazel selectively destroy integrity and anchorage of columnar respiratory epithelial cells, but not of basal cells, in both ex vivo respiratory mucosal explants and in vitro primary equine respiratory epithelial cells (EREC). In turn, this pollen protease-induced damage to respiratory epithelial cell anchorage resulted in increased infection by the host-specific and ancestral alphaherpesvirus equine herpesvirus type 1 (EHV1). Pollen proteases of all three plant species were characterized by zymography and those of white birch were fully identified for the first time as serine proteases of the subtilase family and meiotic prophase aminopeptidase 1 using mass spectrometry-based proteomics. Together, our findings demonstrate that pollen proteases selectively and irreversibly damage integrity and anchorage of columnar respiratory epithelial cells. In turn, alphaherpesviruses benefit from this partial loss-of-barrier function, resulting in increased infection of the respiratory epithelium.

We examined anemia and malaria as risk factors for Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity and antibody levels in a long-standing rural Ugandan cohort, in which KSHV is prevalent. Samples from 4134 children, aged 1-17 years, with a sex ratio of 1:1, and 3149 adults aged 18-103 years, 41% of whom were males, were analyzed. Among children, malaria infection was associated with higher KSHV prevalence (61% vs 41% prevalence among malaria infected and uninfected, respectively); malaria was not assessed in adults. Additionally, lower hemoglobin level was associated with an increased prevalence of KSHV seropositivity, both in children and in adults.

Kaposi's sarcoma-associated herpesvirus (KSHV) can cause several human cancers, including primary effusion lymphoma (PEL), which frequently occur in immunocompromised patients. KSHV-infected patients often suffer from polymicrobial infections caused by opportunistic bacterial pathogens. Therefore, it is crucial to understand how these coinfecting microorganisms or their secreted metabolites may affect KSHV infection and the pathogenesis of virus-associated malignancies. Quorum sensing (QS), a cell density-based intercellular communication system, employs extracellular diffusible signaling molecules to regulate bacterial virulence mechanisms in a wide range of bacterial pathogens, such as Pseudomonas aeruginosa , which is one of the most common opportunistic microorganisms found in immunocompromised individuals. In this study, we evaluated and compared the influence on PEL growth and the host/viral interactome of the major QS signaling molecules [ N -(3-oxododecanoyl)-l-homoserine lactone (OdDHL), N -butyrylhomoserine lactone (BHL), and 2-heptyl-3-hydroxy-4-quinolone (PQS)] in conditioned medium from wild-type (wt) and QS mutant laboratory strains as well as clinical isolates of P. aeruginosa Our data indicate that P. aeruginosa coinfection may facilitate virus dissemination and establishment of new infection and further promote tumor development through effectively inducing viral lytic gene expression by its QS systems. IMPORTANCE Currently, most studies about KSHV infection and/or virus-associated malignancies depend on pure culture systems or immunodeficient animal models. However, the real situation should be much more complicated in KSHV-infected immunocompromised patients due to frequent polymicrobial infections. It is important to understand the interaction of KSHV and coinfecting microorganisms, especially opportunistic bacterial pathogens. Here we report for the first time that P. aeruginosa and its quorum-sensing signaling molecules display a complicated impact on KSHV-associated lymphoma growth as well as the intracellular host/viral gene expression profile. Our data imply that targeting of coinfecting pathogens is probably necessary during treatment of virus-associated malignancies in these immunocompromised patients., (Copyright © 2018 American Society for Microbiology.)

Purpose: Viral infections represent a serious threat for patients after liver transplantation (LT). The identification of risk factors during the early post-transplant period might help to improve prevention of viral infections after LT., Methods: Between 2004 and 2010, 530 adult patients underwent LT at a large university hospital serving a metropolitan region in Europe. This retrospective single-centre study analysed putative risk factors for early viral infections with herpes simplex virus-1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), hepatitis A/B/C (HAV/HBV/HCV) and cytomegalovirus (CMV) in the first 3 months after LT., Results: The final analysis included 501 patients of whom 126 (25.1%) had documented viral infections after LT. No significant differences could be detected between patients with or without viral infections concerning 30- and 90-day mortality. Risk factors in the early post-transplant period identified by multivariate analysis included female gender (CMV, HSV-1), the post-operative need for continuous veno-venous hemofiltration (CMV), septic shock (CMV), detection of fungi (CMV) and the intraoperative amount of transfused blood (EBV)., Conclusions: Enhanced vigilance regarding opportunistic infections is crucial in the management of this high-risk population of immunocompromised patients. In particular, attention should be paid to avoidable conditions that increase the risk of renal replacement therapies in the post-LT setting, especially among women., Trial Registration: DRKS00010672 on German Clinical Trial Register.

Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects. Mice transplanted with CD4-Cre-driven dominant-negative Notch transcriptional regulator Mastermind-Like (CD4-Cre-DNMAML (CCD) mice) bone marrow displayed elevated IL-17 and transforming growth factor-β (TGF β) in the lungs, a further expansion of T-helper type 17 (Th17) cells, and developed more fibrosis than wild-type (WT)-BMT mice. Culture of BMT lung leukocytes with recombinant Notch ligand, DLL4, restored Notch signaling and decreased production of IL-17. Adoptive transfer of CD11c+ DCs could restore Th1 and limit Th17 in WT-BMT but not CCD-BMT mice, indicating that a specific DC/CD4+ T-cell Notch interaction modulates IL-17 production following reconstitution in syngeneic BMT mice. Given recent clinical observations showing that patients with pulmonary complications post-transplant harbor occult herpesvirus infections, these data provide mechanistic insight and suggest potential therapies for these devastating conditions.

Background: Caprine herpesvirus 1 (CpHV-1) causes neonatal mortality and reproductive failure in goats. Despite its impact on herd reproductive performance, few studies have investigated the risk factors associated with CpHV-1 infection. The aim of this cross-sectional study was to identify potential herd- and host-level risk factors associated with CpHV-1 prevalence in a goat population with heterogeneous seropositivity for CpHV-1., Results: Blood samples and individual data from 4542 goats were collected from 255 herds in Piedmont, Italy. Enzyme-linked immunosorbent assay (ELISA) and serum neutralization tests were carried out to detect antibodies against CpHV-1. A mixed-effects model was applied to identify any statistical association between CpHV-1 seropositivity and a set of putative host-level and herd-level risk factors. A total of 630 samples tested were found positive by ELISA (prevalence = 13.9%; 95% confidence interval (CI) 12.9-14.9). Of the 255 tested herds, 85 were classified as positive for the presence of at least one gB-positive animal (herd prevalence 33.3%, 95% CI 27.5-39.2), with a within-herd prevalence between 0.7 and 100% (Q1 = 17.6%; median = 32.3%; Q3 = 50%) (Q = quartiles). The prevalence ratios showed a statistical association with the following risk factors: breeds other than Saanen, older age, larger herd size, meat and extensive herds, and co-existence of CAEV-infected animals., Conclusions: Results from this cross sectional study may help to elucidate the natural history of the infection and inform targeted strategies to control a disease with a potentially important impact on animal health and goat farming economy.

Objective of the study was to determine the effectiveness of various groups of hepatoprotectors in the treatment of patients with nonalcoholic steatohepatitis (NASH) sufferers of the accident at the Chornobyl NPP following the assessment of metabolic changes and control of persistent infections., Materials and Methods: The study included 104 males with NASH, who were sufferers of the Chornobyl disaster and underwent examination and treatment in the conditions of the clinics of the National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine. Analysis of the course of the functional state of the liver before and after treatment with hepatoprotectors was carried out using laboratory methods of investiga tion., Results: Hepatoprotectors of different groups used for the treatment of patients affected by the Chornobyl accident with NASH, differed in their effect on various chains in the pathogenesis of disease. Ursodeoxycholic acid (UDCA) drugs and preparations of holy thistle normalized the functional state of the liver and disorders of fat metabolism. Treatment with essential phospholipids eliminated cytolytic syndrome with a significant decrease in alanine amino transferase (p < 0.05), but increased alkaline phosphatase (p < 0.001), beta lipoproteins (p < 0.05), triglycerides (p < 0.05), the total cholesterol level remained elevated to (7.0 ± 0.8) mmol/L. Amino acid (AA) preparations normal ized the level of aminotransferases, eliminated the symptoms of cholestasis with a significant decrease in bilirubin (p < 0.001) and alkaline phosphatase (p < 0.001), positively influenced on fat and carbohydrate metabolism decreasing levels of beta lipoproteins (p < 0.05), triglycerides and glucose. Treatment with hepatoprotectors posi tively influenced on the state of antioxidant protection (AOP) - decreased before treatment in 56.5 % of patients, after treatment it reduced to 28.6 % (p < 0.05), the number of patients with elevated lipid peroxidation indices decreased from 39.1 % to 21.4 %. Titres of antibodies to persistent herpes virus infections, elevated before treat ment, under the influence of hepatoprotectors did not decrease to reference values., Conclusion: The most effective were drugs on the basis of AA, when applied they normalized the functional state of the, fat and carbohydrate metabolism, decreased lipoperoxidation and improved AOP state. Effect of drugs AA and UDCA on the level of antibodies to herpesvirus infection requires further study., (O. V. Gasanova, E. O. Sarkisova, A. A. Chumak, L. M. Ovsyannikova, O. V. Nosach, L. M. Alohina, V. A. Gasanov, V. V. Kryzhanivska.)

Objective: Burn-related immunosuppression can promote human herpesviridae infections. However, the effect of these infections on morbidity and mortality after pediatric burn injuries is unclear., Methods: We retrospectively analyzed pediatric patients with burns ≥10% of the total body surface area (TBSA) who were admitted between 2010 and 2015. On clinical suspicion of a viral infection, antiviral therapy was initiated. Viral infection was confirmed via Tzanck smear, viral culture, and/or PCR. Study endpoints were mortality, days of antiviral agent administration, type of viral test used, type of viral infection, and length of hospitalization., Results: Of the 613 patients were analyzed, 28 presented with clinically diagnosed viral infections. The use of Tzanck smears decreased over the past 5 years, whereas PCR and viral cultures have become standard. Patients with viral infections had significantly larger burns (53±15% vs. 38±18%, p<0.001); however, length of stay per TBSA burn was comparable (0.5±0.4 vs. 0.6±0.2, p=0.211). The most commonly detected herpesviridae was herpes simplex virus 1. Two patients died due to sepsis, which was accompanied by HSV infection. The mortality rate among all patients (2.7%) was comparable to that in the infected group (7.1%, p=0.898). Acyclovir was given systemically for 9±8days (N=76) and/or topically for 9±9days for HSV (N=39, combination of both N=33). Ganciclovir was prescribed in three cases for CMV., Conclusions: Viral infections occur more commonly in patients suffering from larger burns, and HSV infections can contribute to mortality., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To study factors influencing oro-facial herpetic eruptions (HEs) in patients undergoing retromastoid suboccipital craniectomy for vestibular schwannomas (VS)., Methods: A retrospective analysis of the prospectively collected database (from July 2014 to December 2015). A total of 87 patients underwent retromastoid suboccipital craniectomy for VS at our center. For the purpose of analysis the patient subset was divided into 2 groups, HE and non-HE. Pearson χ 2 test or Fisher exact test were used to identify the factors., Results: The overall incidence of postoperative HE was less than 1% (0.89%, 26 patients of 2916 cases); whereas after VS surgery, it was 20.69% (18 of 87). Demographic profiles of patients in the 2 groups were comparable. Average tumor size (with HE 3.19 ± 2 × 0.67 cm, non-HE 3.38 ± 2 × 1.07 cm), consistency, and laterality also were comparable between the 2 groups. Factors favoring development of postoperative HEs were large size (12 vs. 22, P = 0.013) and preoperative trigeminal nerve (CN V) involvement (9 of 18, 50%, P = 0.046). All patients developed HE in maxillary division of trigeminal nerve (V2), whereas involvement of ophthalmic (V1) and mandibular (V3) divisions were involved less commonly in combination with V2 (V2, 72.2%; V2 + V3, 22.2%; V1 + V2 + V3, 5.6%). The majority of the patients (55.56%) developed HE on postoperative day 3 and none beyond postoperative day 5. All patients responded to empirical oral acyclovir., Conclusions: The study highlights the relatively high incidence and factors associated with this rare but benign complication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

After schwannoma resection, reactivation of herpes infections were reported. Also, IgM antibody titers against Herpes viri increase among 30% of patients, who develop fascial palsy following schwannoma resection. Merlin interacts with p53 pathway and seems to function as a suppressor of viral propagation. Loss of merlin may increase viral particles in nerve fascicles, yet these may fail to cause infections due to immunostimulation by other aberrant antigens present in schwannoma cells. Removal of schwannomas may decrease the antigenic diversity and trigger viral recrudescence. Understanding the viral etiology - molecular merlin interactions in schwannoma tissues may also help to develop strategies against delayed fascial palsy seen following schwannoma resection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread highly toxic environmental contaminant, suppresses immune response and leads to an increased susceptibility to infectious agents. In particular, several studies have provided evidence that TCDD decreases resistance to numerous viruses. Indeed, in vivo and in vitro investigations showed that the presence of TCDD is able to interfere with the replication of both human and animal viruses, such as influenza A viruses, coxsackie virus B3, immunodeficiency virus type-1 (HIV-1), cytomegalovirus (CMV), herpes simplex II, and bovine herpesvirus 1. Moreover, TCDD could induce an exacerbation of latent infection produced by HIV-1, CMV or Epstein-Barr virus. In this review, we first describe the general effects of TCDD exposure on mammalian cells, then we focus on its influence on the viral infections. Overall, the available data support the concept that TCDD exposure may act as an additional risk factor in promoting of viral diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Varicella-zoster virus (VZV) vasculopathy produces stroke, giant cell arteritis, and granulomatous aortitis, and it develops after virus reactivates from ganglia and spreads transaxonally to arterial adventitia, resulting in persistent inflammation and pathological vascular remodeling. The mechanism(s) by which inflammatory cells persist in VZV-infected arteries is unknown; however, virus-induced dysregulation of programmed death ligand 1 (PD-L1) may play a role. Specifically, PD-L1 can be expressed on virtually all nucleated cells and suppresses the immune system by interacting with the programmed cell death protein receptor 1, found exclusively on immune cells; thus, downregulation of PD-L1 may promote inflammation, as seen in some autoimmune diseases. Both flow cytometry and immunofluorescence analyses to test whether VZV infection of adventitial cells downregulates PD-L1 showed decreased PD-L1 expression in VZV-infected compared to mock-infected human brain vascular adventitial fibroblasts (HBVAFs), perineural cells (HPNCs), and fetal lung fibroblasts (HFLs) at 72 h postinfection. Quantitative RT-PCR analyses showed no change in PD-L1 transcript levels between mock- and VZV-infected cells, indicating a posttranscriptional mechanism for VZV-mediated downregulation of PD-L1. Flow cytometry analyses showed decreased major histocompatibility complex class I (MHC-I) expression in VZV-infected cells and adjacent uninfected cells compared to mock-infected cells. These data suggest that reduced PD-L1 expression in VZV-infected adventitial cells contribute to persistent vascular inflammation observed in virus-infected arteries from patients with VZV vasculopathy, while downregulation of MHC-I prevents viral clearance., Importance: Here, we provide the first demonstration that VZV downregulates PD-L1 expression in infected HBVAFs, HPNCs, and HFLs, which, together with the noted VZV-mediated downregulation of MHC-I, might foster persistent inflammation in vessels, leading to pathological vascular remodeling during VZV vasculopathy and persistent inflammation in infected lungs to promote subsequent infection of T cells and hematogenous virus spread. Identification of a potential mechanism by which persistent inflammation in the absence of effective viral clearance occurs in VZV vasculopathy and VZV infection of the lung is a step toward targeted therapy of VZV-induced disease., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Cytomegalovirus (CMV) reactivation leads to obvious morbidity and mortality in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Current immunosuppressive therapy reduces the frequency of graft-versus-host disease (GVHD), and is generally accepted as a high risk factor for viral recurrence. In the present study, we investigated the influence of cyclosporin A (CsA) and rapamycin (RAPA), two commonly used immunosuppressive agents, on murine cytomegalovirus (MCMV) recurrence by two allo-HCT models: one with mild and one with severe GVHD. In models with mild GVHD and partial immune recovery, transplanted mice with CsA and RAPA showed a higher viral load and impaired CMV-specific immune recovery compared to those with placebo. In contrast, in HCT models with severe GVHD, groups treated with immunosuppressive therapy showed alleviation of viral recurrence as well as GVHD-related symptoms. In addition, no CMV-specific immune reconstitution was found in any group, implying immunosuppressive therapy was not relevant to antiviral response. Furthermore, a significant correlation between MCMV DNA copies and tumor necrosis factor alpha (TNF-α) was found, and recipients with immunosuppressive therapy showed a lower level of TNF-α. Finally, using lenalidomide (an inhibitor of TNF-α), a lower viral load was found in animals with lenalidomide. Having received lenalidomide, recipients showed no statistical difference in viral load between groups with and without immunosuppressive therapy. Taken together, we provide evidence of the dual effect of immunosuppressive therapy on viral reactivation. Importantly, we found that immunosuppressive therapy had the ability to alleviate viral load by reducing TNF-α in a mouse model with severe GVHD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of some of these infections on transplant outcomes is still unclear. A prospective survey on the incidence and clinical features of herpesviruses infections after HSCT has not yet been conducted in Brazilian patients, and the impact of these infections on HSCT outcome remains unclear., Methods: We prospectively analyzed the incidence of infection of the eight human herpesviruses simultaneously in 1 045 peripheral blood samples from 98 allogeneic HSCT recipients. Samples were collected weekly starting at the time of transplant until day +100. All herpesviruses were screened and quantified in plasma by quantitative real-time polymerase chain reaction. Median follow up time was 24 months., Results: The incidences of infection for each herpesvirus were as follows: cytomegalovirus (CMV), 44%; human herpesvirus [HHV] 6, 18%; HHV8, 6%; Epstein-Barr virus, 3%; herpes simplex virus 1, 3%; varicella zoster virus, 3%; HHV7, 2%; and herpes simplex virus 2, 1%. The CMV infection was significantly more frequent among adults and was associated with a higher risk of developing acute graft-versus-host disease. The HHV6 infection was significantly more frequent after umbilical cord blood transplant and was associated with an increased risk of platelet engraftment failure. There was no significant impact of these infections on the other transplant outcomes., Conclusions: Herpesviruses infections were uncommon after HSCT, except for CMV and HHV6, which, although relatively frequent, had no clinically relevant impact on the outcomes.

Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The effect of herpesvirus infections in human cytomegalovirus (HCMV)-seropositive (IgG-positive/IgM-negative) HSCT recipients remains poorly understood. The risk factors associated with Epstein-Barr virus (EBV), HCMV, and human herpes virus type 6 (HHV-6) infections after HSCT, both alone and in combination, were investigated in this study., Methods: Peripheral blood specimens were collected from 44 HSCT recipients and examined for viral DNA using quantitative fluorescence PCR assays. Risk factors for EBV, HCMV, and HHV-6 infections were analyzed by binary logistic regression, and relationships between these viruses were analyzed using the Chi-square test., Results: EBV, HCMV, and HHV-6 were detected in 50%, 45.45%, and 25% of HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients, respectively. Male sex (p=0.007) and conditioning regimens including anti-thymocyte globulin (ATG) (p=0.034) were strongly associated with an increased risk of EBV infection. Graft-versus-host disease (GVHD) prophylaxis with corticosteroids was a risk factor for both EBV (p=0.013) and HCMV (p=0.040) infections, while EBV infection (p=0.029) was found to be an independent risk factor for HHV-6 infection. Pre-existing HHV-6 infection was associated with lower rates of HCMV infection (p=0.002); similarly, pre-existing HCMV infection was protective against HHV-6 infection (p=0.036)., Conclusions: HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients exhibited a high rate of herpesvirus infections, particularly EBV. ATG and male sex were strongly associated with an increased risk of EBV infection. GVHD prophylaxis with prednisone was found to affect both EBV and HCMV infections. Prior infection with EBV was shown to promote HHV-6 infection. Taken together, these data highlight the need for active monitoring of herpesvirus infections in patients undergoing HSCT., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

B virus is endemic in macaque monkeys, which are frequently used for research studies. B virus is a risk for every employee working with macaque monkeys, their tissues or cells. Although the risk for B virus infection is low, the risk of death or permanent neurological deficit is high if an exposure is not promptly evaluated and treated. Researcher training, routine use of personal protective equipment, first aid protocols, and prompt reporting to a provider knowledgeable about B virus treatment are essential to prevent this 70% lethal infection in untreated humans. This article presents the history and pathogenesis of B virus, first aid, treatment, and prevention., (© 2015 The Author(s).)

Patients with rheumatoid arthritis are increasingly being treated with different drugs (both non-biologic and biologic disease-modifying anti-rheumatic drugs - DMARDs) that may have immunomodulatory, cytotoxic, or immunosuppressive effects; in particular, anti-tumour necrosis factor (TNF) agents are raising major concern as regards safety issues. An increased risk of infections has been extensively reported during anti-TNF treatment, owing to the primary role of TNF in host defense and immune responses. Although in clinical practice cases of reactivation of varicella zoster virus (VZV) infections during therapy with TNF inhibitors commonly occur, the knowledge on this topic deriving from randomised clinical trials is limited. In this narrative review we focus on the pathophysiology of VZV infection and the role of TNF, and report the available data about VZV outbreaks recorded on Registries of rheumatic patients treated with anti-TNF agents. Finally, we discuss screening strategies and promising preventive measures against VZV infection.

The article presents data of virology examination of recipients of kidney in respect of actual agents of viral infections--cytomegalovirus, Epshtein-Barr virus, viruses of human herpes simplex type I and II, virus of human herpes type VI, Varicella-zoster virus, parvovirus B19, adenoviruses and BK virus. The dynamics of development of infectious processes were analyzed for dominating viral infections during 12 months after organ transplantation. The etiologic structure of viral complications in recipients of kidney was identified. The dominating role of cytomegalovirus, Epshtein-Barr virus, BK virus infections (41.9, 30.4 and 17.5% correspondingly) was established. The algorithm of implementation of virology examination of donors and recipients with indication of evaluation of obtained data and recommendations for its application.

Background: While immunosuppressive therapy for acute graft-versus-host disease (aGVHD) advances, viral reactivation has been found to be an increasingly common complication in these patients. Dermatologists may often be consulted on inpatient services for evaluation., Objective: We investigated the literature for the role of viral infections in aGVHD and review the current evidence regarding management., Methods: Articles in the public domain regarding aGVHD, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses, parvovirus B19, and respiratory viruses were included., Results: Dermatologic findings vary between different viral antigens, and some infections may be a marker for the development of aGVHD or worsen prognosis., Limitations: The heterogeneous cohorts of the studies reviewed often preclude direct comparison between results., Conclusion: The relationship between viral reactivation and aGVHD may be bidirectional and is worthy of further exploration. Additional studies are needed to determine appropriate prophylaxis and treatment., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Preventive healthcare recommendations for zoo felids include vaccination against primary viral diseases that affect domestic felids. Although associated with a more-substantial immune response in their domestic counterparts, use of modified live virus vaccines (MLV) in nondomestic carnivores can result in vaccine-induced viral disease. This case report details a feline herpesvirus and calicivirus outbreak in two black-footed cat (Felis nigripes) kittens and their dam following use of an MLV in the kittens. Clinical signs included anorexia, nasal discharge, sneezing, and tachypnea. Patient history, clinical signs, real-time polymerase chain reaction results, and histopathologic evaluation of tissues confirmed the diagnosis. Although unable to definitively prove that the disease observed in these cases was caused by the MLV, there is strong temporal and circumstantial evidence that this was the case. This outbreak of feline upper respiratory infection following vaccination with a multivalent MLV resulted in significant morbidity and mortality, serving as an important reminder that recombinant or killed vaccines are the safest choice for use in nondomestic species, particularly in kittens.

The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 10(6)/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT., (© 2014 S. Karger AG, Basel.)

Although originally described in Staphylococcus aureus, resistance among bacteria has now become a race to determine which classes of bacteria will become more resistant. Availability of antibacterial agents has allowed the development of entirely new diseases caused by nonbacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. This article presents the growing body of knowledge of the herpes family of viruses, and their occurrence and consequences in patients with concomitant surgical disease or critical illness. The focus is on previously immunocompetent patients, as the impact of herpes viruses in immunosuppressed patients has received thorough coverage elsewhere., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus. Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental, and immunologic factors. These factors likely account for the heterogeneity of AD onset and the severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved through early interventions to protect the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention might improve long-term outcomes for AD and reduce the systemic allergen sensitization that leads to associated allergic diseases in the gastrointestinal and respiratory tract., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: TNF blockers have demonstrated efficacy in inflammatory rheumatic diseases (IRDs). The drugs are associated with a moderate but definite risk of bacterial infection, but risk of viral infection is not clearly known., Objective: To assess the risk of herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA) receiving TNF blockers as compared with DMARDs., Methods: A systematic search of literature up to March 2013 was performed, in MEDLINE, EMBASE, the Cochrane library and abstracts from the ACR and EULAR congresses from 2008 to 2011. Studies were included if they reported the incidence of HZ, respectively, in patients receiving anti-TNF and conventional DMARDs., Results: The literature search identified 3446 articles and 88 congress abstracts; a manual search retrieved seven articles. Finally, 26 articles and nine abstracts were included; six articles and one abstract were of meta-analyses estimating the relative risk of HZ in patients with RA with a total follow-up of 163,077 patient-years. From the meta-analyses of data for seven registries, the pooled risk ratio for HZ with TNF blockers was 1.61 [95% CI 1.16-2.23] (P = 0.004). Proportions of severe HZ ranged from 4.9% to 20.9% with TNF-blockers and from 2.0% to 5.5% with conventional DMARDs, in the different registries., Conclusions: This meta-analysis revealed a significantly increased risk of HZ, up to 61%, in patients with IRD receiving TNF blockers. These data raise the issue of systematic prophylactic treatment with known history of HZ or vaccination without this history., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Three NOD2 polymorphisms (single nucleotide polymorphism [SNP]8 [2104C>T, Arg702Trp], SNP12 [2722G>C, Gly908Arg], and SNP13 [3020insC, Leu1007 fsins C]), identified as disease-associated variants in Crohn's disease, have recently been suggested as gene markers of the outcome of hematopoietic stem cell transplantation (HSCT). In the present multicenter study of 464 donor-recipient pairs, we focused on the effect of NOD2 mutation(s) on the risk of infections and acute graft-versus-host disease (aGVHD). The presence of SNP13 in recipients, donors, or both was more frequently seen in patients having sepsis than in those lacking sepsis (9 of 48 versus 33 of 386, P = .046). The presence of SNP8 (recipient and/or donor positive) was associated with a higher rate of Herpes viruses reactivation (17 of 21 versus 86 of 173, P = .007). In the SNP8-positive group, a trend for a higher rate of bacteremia well controlled by antibiotics was found (9 of 10 versus 47 of 81, P = .106). In contrast, the presence of SNP13 in recipient and/or donor resulted in a poor response to antibiotics (5 of 11 versus 9 of 10, P = .042). A statistically significant association between the presence of NOD2 SNPs and acute grade > II GVHD was found in a subgroup of HSCT patients who received transplants from unrelated donors with a myeloablative conditioning regimen that included antithymocyte globulin (ATG). In this subgroup of patients, donor positivity for any SNPs investigated (7 of 18 versus 17 of 113, P = .036) and, independently, only the presence of SNP8 (4 of 8 versus 20 of 123, P = .055) were associated with severe grade ≥ II aGVHD. In conclusion, SNP8 positivity in donors or recipients makes patients more prone to Herpes viruses reactivation and bacteremia but not to sepsis. Septic complications were associated with SNP13 polymorphism. SNP8 in donors constitutes a risk factor of severe aGVHD, but only if patients received transplants from unrelated donors and received ATG as part of a conditioning regimen., (Copyright © 2014. Published by Elsevier Inc.)

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.

Human herpesviruses (HHV) 6 and 7 are ubiquitous infections that reactivate commonly in transplant recipients. However, clinical diseases due to these viruses are reported only in 1% of solid organ transplant recipients. Fever, rash and bone marrow suppression are the most common manifestations, but symptoms of tissue invasive disease may be observed. Treatment of HHV-6 and HHV-7 disease includes antiviral therapy and cautious reduction in immunosuppression. HHV-8 is an oncogenic gamma-herpesvirus that causes Kaposi's sarcoma, Castleman's disease and primary effusion lymphomas in transplant recipients. Nonmalignant diseases such as bone marrow suppression and multiorgan failure have also been associated with HHV-8. Reduction in immunosuppression is the first line treatment of HHV-8 infection. Other alternatives for treatment, especially for HHV-8 diseases not responsive to immuno-minimization strategies, are surgery and chemotherapy. Sirolimus has been shown to be a beneficial component for the treatment of Kaposi's sarcoma and the role of antivirals for HHV-8 infection is being investigated., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: We assessed the morbidity of herpesviruses in patients with type 1 diabetes mellitus (T1D) enrolled in immunosuppressive treatment studies., Methods: Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) infections were monitored in 126 participants of a randomized, double-blind, placebo-controlled study of daclizumab (DZB) and mycophenolate mofetil (MMF) including DZB(+)MMF(+), DZB(-)MMF(+), DZB(+)MMF(-), and DZB(-)MMF(-). During the 2-year follow-up, herpesviral infections were monitored clinically, by serology and blood DNA polymerase chain reaction., Results: Among 57 baseline EBV-seronegative participants, 9 developed EBV primary infections, including 2 with infectious mononucleosis syndrome. There were no appreciable differences in the course of the primary EBV infections across treatment groups. Among 69 baseline EBV-seropositive participants, 22 had virologic reactivations, including 1 symptomatic DZB(-)MMF(+) subject. Compared with 7 DZB(-)MMF(-) EBV reactivators, the 9 DZB(+)MMF(+) reactivators tended to have more prolonged viremia (11.4 vs 4.4 months; P = .06) and higher cumulative viral burden (14.2 vs 12.5 log EBV copies/mL; P = .06). Four of 85 baseline CMV-seronegative subjects developed asymptomatic primary CMV infections. There were no CMV reactivations. Of 30 baseline HSV-seropositive subjects, 8 developed ≥1 episode of herpes labialis; 1 subject had a primary HSV infection; and 1 subject without baseline serology information had a new diagnosis of genital HSV. There were no significant differences in the incidence of HSV recurrences across treatment groups. Of 100 baseline VZV-seropositive subjects, 1 DZB(-)MMF(-) subject developed herpes zoster and 1 DZB(-)MMF(+) subject had Bell's palsy possibly related to VZV., Conclusions: The use of DZB alone or in combination with MMF was not associated with increased morbidity due to herpesviruses., Clinical Trials Registration: NCT00100178.

HHV-8 is a herpes virus discovered in 1994 in Kaposi sarcoma cells. Its involvement was later demonstrated in multicentric Castleman disease and in primary lymphoma effusion lymphoma. These diseases arise almost exclusively in immunocompromised patients, mostly in association with HIV infection. Apart from Kaposi's sarcoma, combined antiretroviral therapy does not seem to have reduced the incidence of these diseases, which remain rare. In these three diseases, pulmonary involvement is common and may be the presenting feature. Kaposi's sarcoma of the lung is usually asymptomatic but may require specific therapy. Pulmonary involvement is mostly associated with cutaneous disease. Patients with Castleman disease typically present with fever and lymphadenopathy, associated with interstitial lung disease without opportunistic infection. Patients with primary lymphoma effusion presents with fever and an exudative lymphocytic pleural effusion, without a pleural mass on the CT-scan. Rapid diagnosis of these conditions avoids unnecessary invasive examinations and leads to prompt specific treatment., (© 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.)