Management of Oral Manifestations of Herpes Simplex Virus, Varicella Zoster Virus, and Human Papillomavirus.

Human herpes virus is a family of DNA viruses that includes herpes simplex virus (HSV) and varicella zoster virus (VZV). HSV-1 and HSV-2 are fairly common and result in oral and genital lesions. Recurrent infections of herpes include lesions on the lips resulting in pain and possibly societal stigma, making adequate treatment of these conditions crucial. VZV is the cause of chicken pox and shingles. Acyclovir and other nucleoside analogues have been the gold standard of treatment for HSV and VZV, but newer, more effective treatments are being developed, which is beneficial regarding the issue of resistance to standard antivirals. Human papillomavirus (HPV) is also a DNA virus with different subtypes that result in four common oral benign lesions. The significance and treatments of HSV, VZV, and HPV are discussed, along with certain developing treatments of herpes labialis (HSV).

Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

PCR testing for herpesviruses in aqueous humor samples from patients with and without clinical corneal endothelial graft rejection.

To compare prevalence of positive PCR tests for herpesviruses between patients with and without a history of clinical corneal endothelial allograft rejection (AGR). Retrospective cross-sectional study with two-group comparison. A total of 307 aqueous humor (AH) samples from 235 Patients and 244 eyes who underwent penetrating keratoplasty or Descemet membrane endothelial keratoplasty or had a diagnostic AH aspiration due to clinical AGR between 2019 and 2023 were tested for DNA of herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). PCR test results were compared between the two groups (with/without AGR). Another sub-analysis examined the results of patients without a history of herpetic keratitis. A total of 8% of eyes with clinical AGR (9/108) had a positive PCR result for one of the herpesviruses (HSV:3, CMV:3, EBV:2, VZV:1). All patients in the group without AGR had negative PCR results for all previous viruses (0/136). The difference was statistically significant (p < 0.001). The sub-analysis of eyes without a history of herpetic keratitis also revealed significantly more positive herpes PCR results (7/87) in eyes with AGR than in eyes without AGR (0/42, p = 0.005). Clinical AGR after keratoplasty shows a significant correlation to viral replication. Herpetic infection and AGR could occur simultaneously and act synergistically. Timely differentiation between active herpetic infection and/or AGR is pivotal for proper treatment and graft preservation.

Oncolytic varicella-zoster virus engineered with ORF8 deletion and armed with drug-controllable interleukin-12.

BACKGROUND: The varicella-zoster virus (VZV), belonging to the group of human α-herpesviruses, has yet to be developed as a platform for oncolytic virotherapy, despite indications from clinical case reports suggesting a potential association between VZV infection and cancer remission. METHODS: Here, we constructed oncolytic VZV candidates based on the vaccine strain vOka and the laboratory strain Ellen. These newly engineered viruses were subsequently assessed for their oncolytic properties in the human MeWo melanoma xenograft model and the mouse B16-F10-nectin1 melanoma syngeneic model. RESULTS: In the MeWo xenograft model, both vOka and Ellen exhibited potent antitumor efficacy. However, it was observed that introducing a hyperfusogenic mutation into glycoprotein B led to a reduction in VZV's effectiveness. Notably, the deletion of ORF8 (encodes viral deoxyuridine triphosphatase) attenuated the replication of VZV both in vitro and in vivo, but it did not compromise VZV's oncolytic potency. We further armed the VZV Ellen-ΔORF8 vector with a tet-off controlled mouse single-chain IL12 (scIL12) gene cassette. This augmented virus was validated for its oncolytic activity and triggered systemic antitumor immune responses in the immunocompetent B16-F10-nectin1 model. CONCLUSIONS: These findings highlight the potential of using Ellen-ΔORF8-tet-off-scIL12 as a novel VZV-based oncolytic virotherapy.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Impaired STING Activation Due to a Variant in the E3 Ubiquitin Ligase AMFR in a Patient with Severe VZV Infection and Hemophagocytic Lymphohistiocytosis.

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus exclusively infecting humans, causing two distinct pathologies: varicella (chickenpox) upon primary infection and herpes zoster (shingles) following reactivation. In susceptible individuals, VZV can give rise to more severe clinical manifestations, including disseminated infection, pneumonitis, encephalitis, and vasculopathy with stroke. Here, we describe a 3-year-old boy in whom varicella followed a complicated course with thrombocytopenia, hemorrhagic and necrotic lesions, pneumonitis, and intermittent encephalopathy. Hemophagocytic lymphohistiocytosis (HLH) was strongly suspected and as the condition deteriorated, HLH therapy was initiated. Although the clinical condition improved, longstanding hemophagocytosis followed despite therapy. We found that the patient carries a rare monoallelic variant in autocrine motility factor receptor (AMFR), encoding a ubiquitin ligase involved in innate cytosolic DNA sensing and interferon (IFN) production through the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway. Peripheral blood mononuclear cells (PBMCs) from the patient exhibited impaired signaling downstream of STING in response dsDNA and 2'3'-cGAMP, agonists of cGAS and STING, respectively, and fibroblasts from the patient showed impaired type I IFN responses and significantly increased VZV replication. Overexpression of the variant AMFR R594C resulted in decreased K27-linked STING ubiquitination compared to WT AMFR. Moreover, ImageStream technology revealed reduced STING trafficking from ER to Golgi in cells expressing the patient AMFR R594C variant. This was supported by a dose-dependent dominant negative effect of expression of the patient AMFR variant as measured by IFN-ß reporter gene assay. Finally, lentiviral transduction with WT AMFR partially reconstituted 2'3'-cGAMP-induced STING-mediated signaling and ISG expression in patient PBMCs. This work links defective AMFR-STING signaling to severe VZV disease and hyperinflammation and suggests a direct role for cGAS-STING in the control of viral infections in humans. In conclusion, we describe a novel genetic etiology of severe VZV disease in childhood, also representing the first inborn error of immunity related to a defect in the cGAS-STING pathway.

Diagnostic Methods and Management Strategies of Herpes Simplex and Herpes Zoster Infections.

Herpesviruses are medium-sized double-stranded DNA viruses. Of more than 80 herpesviruses identified, only 9 human herpesviruses have been found to cause infection in humans. These include herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), human cyto-megalovirus (HCMV), Epstein-Barr virus (EBV), and human herpesvirus (HHV-6A, HHV-6B, HHV-7, HHV-8). HSV-1, HSV-2, and VZV can be problematic given their characteristic neurotropism which is the ability to invade via fusion of its plasma membrane and reside within neural tissue. HSV and VZV primarily infect mucocutaneous surfaces and remain latent in the dorsal root ganglia for a host's entire life. Reactivation causes either asymptomatic shedding of virus or clinical manifestation of vesicular lesions. The clinical presentation is influenced by the portal of entry, the immune status of the host, and whether the infection is primary or recurrent. Affecting 60% to 95% of adults, herpesvirus-associated infections include gingivostomatitis, orofacial and genital herpes,and primary varicella and herpes zoster. Symptomatology, treatment, and potential complications vary based on primary and recurrent infections as well as the patient's immune status.

Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states.

Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Here we describe structure-function studies of the VZV gB DIII central helix targeting residues 526EHV528. Critically, a H527P mutation captures gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] are identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.

Immunogenicity in Mice Immunized with Recombinant Adenoviruses Expressing Varicella-Zoster Virus Envelope Glycoprotein E.

Herpes zoster (HZ) is a disease caused by the reactivation of latent varicella-zoster virus (VZV). The subunit vaccine, Shingrix®, and live attenuated vaccine, Zostavax®, could be used as an HZ vaccine that prevents HZ from being developed due to the reactivation of latent VZV in the sensory ganglia due to aging, stress or immunosuppression. In this study, the recombinant adenoviruses rChAd63/gE expressing glycoprotein E (gE) of VZV based on chimpanzee adenovirus serotype 63 (ChAd63) were constructed and investigated for the immunogenicity of different immune pathways in C57BL/6 mice. The results showed similar CD4+ T and CD8+ T cell responses to Shingrix® were induced in mice vaccinated using rChAd63/gE via different immune pathways. This study elucidates that recombinant adenoviruses expressing VZV gE could be appropriate for further development as a new HZ vaccine candidate via different immune pathways.

Detection of varicella zoster virus DNA in blood from immunocompromised patients during the week preceding the onset of herpes zoster rash.

OBJECTIVE: To assess whether varicella zoster virus (VZV) DNA can be detected in blood before herpes zoster (HZ) rash onset. METHOD: Monocentric retrospective study from January 2019 to March 2023 including patients with HZ and stored blood samples performed during the week preceding the onset of HZ rash. Blood samples were retrospectively analyzed for VZV DNA by quantitative PCR. RESULTS: Among the 138 patients with HZ during the study period, stored blood samples performed during the week preceding the onset of HZ rash were available for 13 of them. Twelve (92 %) patients were immunosuppressed, mostly due to solid organ transplantation (38 %), solid malignancy (31 %) or autoimmune disease (23 %). During the week preceding HZ onset, VZV DNA was detected in blood from 10 (77 %) patients, with a median value of 3.6 log (copies/mL) (IQR 3.3-3.9). At the time of HZ onset, all VZV PCR performed in available blood samples were positive. CONCLUSION: Our findings demonstrates that VZV DNA can be commonly detected in blood from immunocompromised patients during the prodromal phase of HZ. Early screening of VZV DNA in blood from high-risk immunocompromised patients might improve HZ therapeutic management.

Resveratrol: a potential medication for the prevention and treatment of varicella zoster virus-induced ischemic stroke.

BACKGROUND: Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS. OBJECTIVE: By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS. METHODS: In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein-Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations. RESULTS: The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood-brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score. CONCLUSIONS: Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.

Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.

Herpes Zoster Reactivation After mRNA and Adenovirus-Vectored Coronavirus Disease 2019 Vaccination: Analysis of National Health Insurance Database.

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

Herpesviruses reactivation following COVID-19 vaccination: a systematic review and meta-analysis.

BACKGROUND: The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines. METHODS: A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines. RESULTS: Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common. CONCLUSION: In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.

Algorithm for optimized mRNA design improves stability and immunogenicity.

Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. 1-3), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products4. Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression5. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large-for example, there are around 2.4 × 10632 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses insurmountable computational challenges. Here we provide a simple and unexpected solution using the classical concept of lattice parsing in computational linguistics, where finding the optimal mRNA sequence is analogous to identifying the most likely sentence among similar-sounding alternatives6. Our algorithm LinearDesign finds an optimal mRNA design for the spike protein in just 11 minutes, and can concurrently optimize stability and codon usage. LinearDesign substantially improves mRNA half-life and protein expression, and profoundly increases antibody titre by up to 128 times in mice compared to the codon-optimization benchmark on mRNA vaccines for COVID-19 and varicella-zoster virus. This result reveals the great potential of principled mRNA design and enables the exploration of previously unreachable but highly stable and efficient designs. Our work is a timely tool for vaccines and other mRNA-based medicines encoding therapeutic proteins such as monoclonal antibodies and anti-cancer drugs7,8.

Cerebrospinal fluid virology in people with HIV.

OBJECTIVE: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. METHOD: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. RESULTS: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). CONCLUSION: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.

[The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma].

INTRODUCTION: Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. MATERIALS AND METHODS: 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. RESULTS: EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). CONCLUSION: Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Viruses Associated with Acute Conjunctivitis in Vanuatu.

The first manifestation of a viral infection may be conjunctivitis. There are limited data on the etiology of viral conjunctivitis in Vanuatu, a country in the South Pacific Ocean. Patients presenting to one of two Vanuatu health centers with presumed infectious conjunctivitis were eligible if symptom onset was within 14 days of screening. Conjunctival and anterior nasal swabs were obtained and subjected to unbiased RNA deep sequencing (RNA-seq) to identify DNA and RNA viruses. For samples collected from May to November 2021, RNA-seq identified a viral etiology in 12/48 patients. Human adenovirus species were the most common viruses (58%) detected, followed by human herpes viruses (cytomegalovirus, varicella zoster virus, and human herpes 7 virus). Rhinovirus C, Epstein-Barr virus, and bocavirus were also detected. In summary, the etiology for viral conjunctivitis in Vanuatu appears broad. Unbiased testing may be useful for disease surveillance.