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Nuclear egress is an essential process in herpesvirus replication whereby nascent capsids translocate from the nucleus to the cytoplasm. This initial step of nuclear egress-budding at the inner nuclear membrane-is coordinated by the nuclear egress complex (NEC). Composed of the viral proteins UL31 and UL34, NEC deforms the membrane around the capsid as the latter buds into the perinuclear space. NEC oligomerization into a hexagonal membrane-bound lattice is essential for budding because NEC mutants designed to perturb lattice interfaces reduce its budding ability. Previously, we identified an NEC suppressor mutation capable of restoring budding to a mutant with a weakened hexagonal lattice. Using an established in-vitro budding assay and HSV-1 infected cell experiments, we show that the suppressor mutation can restore budding to a broad range of budding-deficient NEC mutants thereby acting as a universal suppressor. Cryogenic electron tomography of the suppressor NEC mutant lattice revealed a hexagonal lattice reminiscent of wild-type NEC lattice instead of an alternative lattice. Further investigation using x-ray crystallography showed that the suppressor mutation promoted the formation of new contacts between the NEC hexamers that, ostensibly, stabilized the hexagonal lattice. This stabilization strategy is powerful enough to override the otherwise deleterious effects of mutations that destabilize the NEC lattice by different mechanisms, resulting in a functional NEC hexagonal lattice and restoration of membrane budding.

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as "monkeypox") given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting. [ABSTRACT FROM AUTHOR]

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as “monkeypox”) given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting.

Introduction. Herpes simplex virus type 1 (HSV-1) is one of the most common human viral infections and has a double-stranded DNA genome belonging to the Herpesviridae family. Smoking is one of the leading causes of disease and premature death worldwide, responsible for the death of up to six million people annually. The purpose of the current study was to determine the seroprevalence of HSV-1 infection among smokers.‎ Methods. The search strategy was conducted in the period from December 2022 to January 2023. The study included a random sample of 94 (88 males, and 6 females) healthy participants, aged between ≤ 20 to ≥ 60 years, with 50 participants as the control group. The HSV serological testing consisted of detecting antibodies to HSV-1 IgG with the help of ELISA. Results. Most participants were university students, consisting of 45.7% males and 5.3% females, followed by employed smokers, consisting of 0.2% males and 1.1% females. The number of females was much lower than that of males reaching 6.4 and 93.6% respectively, due to customs and traditions. The seroprevalence was 24.47, 22.3 and 2.1% in males and females respectively. The seroprevalence rate was 13.8% in hookah and cigarette smokers, 9% in cigarette smokers and 1.1% in hookah smokers exclusively. The highest rate was observed in the age groups of 21-30 and 31–40 years with 12.80% and 7.40% respectively. Conclusions. The study revealed that the seroprevalence of HSV-1 IgG was 24.47%, and was higher among hookah and cigarette smokers compared to those who exclusively smoked cigarettes or hookah.

Purpose: To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). Methods: Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. Results: Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27–43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31–514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). Conclusions: Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up. [ABSTRACT FROM AUTHOR]

The objective of this study is to describe our COVID-19 patients with herpesviridae reactivation in the central nervous system (CNS). Four patients were described including two with acute encephalitis and two with acute encephalomyelitis. Three of four patients had abnormal findings on neuroimaging studies. One of four patients died, one survived with major neurological sequelae, and two others fully recovered. Herpesviridae reactivation in the CNS in patients with COVID-19 is a rare but serious coincidence. The optimal therapeutic management has not been investigated and until more information is available, it is prudent to treat these patients with appropriate antivirals with or without anti-inflammatory agents.

Abstract Background Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization. Methods Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study. Results One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection. Conclusion Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.

Background: Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization. Methods: Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study. Results: One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection. Conclusion: Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP. [ABSTRACT FROM AUTHOR]

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t- tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2–24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6–45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases. [ABSTRACT FROM AUTHOR]

Bats have gained cumulative attention as potential reservoirs for viruses, being crucial to increase our ability to predict viral prevalence and transmissions, as well as support the possible management of future zoonotic episodes. Following the PRISMA standard systematic review protocols, we conducted a comprehensive search worldwide for scientific papers dealing with bat-hosted viruses of the Adenoviridae and Herpesviridae families. The search was completed using the Scopus, CABI, and SciELO, databases of bat-associated viruses of these two families as well as the Google Scholar search engine. Our search comprised a total of 2656 scientific papers. After a thorough review and screening of the papers, we selected for our study a total of 90 papers published between 1996 and 2022. We found marked taxonomic and spatial biases, the most studied bats being predominantly vespertilionids, rhinolophids, phyllostomids, and pteropodids, whereas other families (e.g., Natalidae, Noctilionidae, and Furipteridae) are still lacking information. The most studied areas are southern and east Asia, although there are large areas (north Africa, the Middle East, and all the way to central or northern Asia) still overlooked. Out of the total number of papers, as many as 55 identified bat-hosted Adenovirus (AdV) and 54 papers identified Herpesvirus (HSV). Our revision reveals the presence of AdVs in a total of 97 bat species from 42 genera and 11 families. The presence of HSVs is reported also in 109 bat species from 45 genera and 10 families. Although both AdVs and HSVs in general show a clear host specificity and parallel evolution with their hosts, these results also point to the potential of these viruses to cross, in some cases, species barriers. [ABSTRACT FROM AUTHOR]

Herpesviruses are large DNA viruses that have long been used as powerful gene therapy tools. In recent years, the ability of herpesviruses to stimulate both innate and adaptive immune responses has led to their transition to various applications as vaccine vectors. This vaccinology branch is growing at an unprecedented and accelerated rate. To date, human herpesvirus-based vectors have been used in vaccines to combat a variety of infectious agents, including the Ebola virus, foot and mouth disease virus, and human immunodeficiency viruses. Additionally, these vectors are being tested as potential vaccines for cancer-associated antigens. Thanks to advances in recombinant DNA technology, immunology, and genomics, numerous steps in vaccine development have been greatly improved. A better understanding of herpesvirus biology and the interactions between these viruses and the host cells will undoubtedly foster the use of herpesvirus-based vaccine vectors in clinical settings. To overcome the existing drawbacks of these vectors, ongoing research is needed to further advance our knowledge of herpesvirus biology and to develop safer and more effective vaccine vectors. Advanced molecular virology and cell biology techniques must be used to better understand the mechanisms by which herpesviruses manipulate host cells and how viral gene expression is regulated during infection. In this review, we cover the underlying molecular structure of herpesviruses and the strategies used to engineer their genomes to optimize capacity and efficacy as vaccine vectors. Also, we assess the available data on the successful application of herpesvirus-based vaccines for combating diseases such as viral infections and the potential drawbacks and alternative approaches to surmount them. [ABSTRACT FROM AUTHOR]

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in recipients of haploidentical and fully matched transplantations is on the increase. Published studies have reported an increased incidence of cytomegalovirus (CMV) infection with the use of PTCy. Limited data exist on the incidence and outcomes of infection with non-CMV herpesviruses (NCHV) in this setting. The aim of this study was to evaluate the cumulative incidence of NCHV infections and the association of NCHV infections with transplantation-specific outcomes in recipients of haploidentical transplantation with PTCy (HaploCy), matched sibling donor transplantation with PTCy (SibCy), and matched sibling donor transplantation with calcineurin inhibitor-based prophylaxis (SibCNI). We hypothesized that, like CMV infection, HaploCy recipients of also will have a higher risk of NCHV infections. Using the Center for International Blood and Marrow Transplantation Research database, we analyzed 2765 patients (HaploCy, n = 757; SibCNI, n = 1605; SibCy, n = 403) who had undergone their first hematopoietic stem cell transplantation (HCT) between 2012 and 2017 for acute myelogenous leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. The cumulative incidence of NCHV at 6 months post-NCT was 13.9% (99% confidence interval], 10.8% to 17.3%) in the HaploCy group, 10.7% (99% CI, 7.1% to 15%) in the SibCy group, and 5.7% (99% CI, 4.3% to 7.3%) in the Sib CNI group (P < .001). This was due primarily to a higher frequency of human herpesvirus 6 viremia reported in patients receiving PTCy. The incidence of Epstein-Barr viremia was low in all groups, and no cases of post-transplantation lymphoproliferative disorder were seen in either PTCy group. The incidence of NCHV organ disease was low in all 3 cohorts. The development of NCHV infection was associated with increased treatment-related mortality, particularly in the HaploCy group. There was no association with the development of GVHD, relapse, or disease-free survival. Patients in PTCy cohorts who did not develop NCHV infection had lower rates of cGVHD. This study demonstrates that the use of PTCy is associated with an increased risk of NCHV infection. The development of NCHV infection was associated with increased nonrelapse mortality, especially in the HaploCy group. Prospective trials should consider viral surveillance strategies in conjunction with assessment of immune reconstitution for a better understanding of the clinical relevance of viral reactivation in different HCT settings.

Abstract Background We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU. Methods Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1st March 2020 and 30th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality. Results Out of 431 patients included in the study, bacteremia was present in N = 191 (44.3%) and death occurred in N = 210 (48.7%). After multivariate analysis, increased risk of bacteremia was found for viral reactivation (OR = 3.28; 95% CI:1.83–6.08), pronation (3.36; 2.12–5.37) and orotracheal intubation (2.51; 1.58–4.02). Increased mortality was found for bacteremia (2.05; 1.31–3.22), viral reactivation (2.29; 1.29–4.19) and lymphocytes

This scientific commentary discusses the association between herpes viral infections and the prodromal phase of multiple sclerosis (MS). While the link between Epstein-Barr virus (EBV) infection and MS has been established, the long duration of the prodrome suggests that other factors are at play. The study presented in this commentary explores the association between human herpesvirus 6A (HHV-6A) seropositivity and MS prodrome. The authors found that HHV-6A seropositivity was significantly higher among MS cases compared to controls, and serum neurofilament light chain (sNfL) levels were elevated in both HHV-6A seropositive and seronegative cases. However, the study has methodological limitations, and the causative role of HHV-6A in MS pathogenesis is not proven. Further research is needed to understand the potential role of chronic viral infections in MS and to develop preventive strategies. [Extracted from the article]

Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1–4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27–44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3–7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60–358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95–1.88) for enteroviruses, 1.55 (95% CI 1.00–2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98–2.33) for varicella-zoster virus and 1.37 (95% CI 0.61–3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03–1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. [ABSTRACT FROM AUTHOR]

Background: We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU. Methods: Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1st March 2020 and 30th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality. Results: Out of 431 patients included in the study, bacteremia was present in N = 191 (44.3%) and death occurred in N = 210 (48.7%). After multivariate analysis, increased risk of bacteremia was found for viral reactivation (OR = 3.28; 95% CI:1.83–6.08), pronation (3.36; 2.12–5.37) and orotracheal intubation (2.51; 1.58–4.02). Increased mortality was found for bacteremia (2.05; 1.31–3.22), viral reactivation (2.29; 1.29–4.19) and lymphocytes < 0.6 × 103c/µL (2.32; 1.49–3.64). Conclusions: We found that viral reactivation, mostly due to Herpesviridae, was associated with increased risk of both bacteremia and mortality. In addition, pronation and intubation are strong predictors of bacteremia, which in turn together with severe lymphocytopenia due to SARS-CoV2 was associated with increased mortality. Most episodes of bacteremia, even due to Acinetobacter spp, were not predicted by microbiological evidence of colonization. [ABSTRACT FROM AUTHOR]

Introduction. The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin. Aim of the study: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families. Materials and methods. Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses. Results and discussion. DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified. Conclusion. Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.

Background and aimsAlcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.Approach and resultsWe extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.ConclusionsIn conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.

Bats have gained cumulative attention as potential reservoirs for viruses, being crucial to increase our ability to predict viral prevalence and transmissions, as well as support the possible management of future zoonotic episodes. Following the PRISMA standard systematic review protocols, we conducted a comprehensive search worldwide for scientific papers dealing with bat-hosted viruses of the Adenoviridae and Herpesviridae families. The search was completed using the Scopus, CABI, and SciELO, databases of bat-associated viruses of these two families as well as the Google Scholar search engine. Our search comprised a total of 2656 scientific papers. After a thorough review and screening of the papers, we selected for our study a total of 90 papers published between 1996 and 2022. We found marked taxonomic and spatial biases, the most studied bats being predominantly vespertilionids, rhinolophids, phyllostomids, and pteropodids, whereas other families (e.g., Natalidae, Noctilionidae, and Furipteridae) are still lacking information. The most studied areas are southern and east Asia, although there are large areas (north Africa, the Middle East, and all the way to central or northern Asia) still overlooked. Out of the total number of papers, as many as 55 identified bat-hosted Adenovirus (AdV) and 54 papers identified Herpesvirus (HSV). Our revision reveals the presence of AdVs in a total of 97 bat species from 42 genera and 11 families. The presence of HSVs is reported also in 109 bat species from 45 genera and 10 families. Although both AdVs and HSVs in general show a clear host specificity and parallel evolution with their hosts, these results also point to the potential of these viruses to cross, in some cases, species barriers.

The Herpesviridae family is subdivided into three subfamilies, namely α-herpersvirinae, β-herpesvirinae and γ-herpesvirinae. All members of the family are characterized by a common structure consisting of a large linear double-stranded DNA genetic core packaged into a proteic icosahedral capsid and further enclosed in a phospholipidic bilayer envelope of cellular origin. Herpesviruses are characterized, on one side, by a high stability of the genome during virus replication, however, on the other side by a high capability to change rapidly in response to natural evolutionary selecting pressure. Therefore, there is a continuous emergence and establishment of new viruses. In this contest γ-herpesviruses, whose contribution to disease outbreaks in wildlife population has often been underestimated, pose a serious problem due to their ability to cross species barriers, infect new hosts and give rise to newly emerged viruses or virus variants in reservoirs. The problem is exacerbated by the absence of vaccines and effective treatments, such as for Malignant Catarrhal Fever (MCF) in cattle or MCF-like diseases, caused by the Malignant Catarrhal Fever Viruses (MCFVs). MCFV can infect both livestock and wild animals sporadically, however when it does, it can cause clinical disease with important welfare implications, dramatic pathological changes and often has death as outcome. Due to the inability to isolate the majority of the γ-herpesviruses in vitro, their detection and characterization necessarily involve molecular methodologies aimed at diagnosing, identifying and resolving their phylogenetic origins and the evolutionary relationship with the host species. This information is ultimately necessary to improve the control of the disease spread, and to better identify the source of outbreaks, which can be seriously detrimental to zoological collections, especially for endangered species. This review provides an overview of the currently available methodologies applied for identification and characterization of MCFVs, critically describes benefits and disadvantages of these, recognises the gaps to be addressed and identifies future diagnostic opportunities. [ABSTRACT FROM AUTHOR]

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Objectives: To characterize the oral shedding of herpes viruses in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) and investigate its relationship with clinical outcomes. Materials and Methods: Polymerase chain reaction and enzymatic digestion were performed to identify the oral shedding of the members of the Herpesviridae family in 31 patients. The samples were collected from the oral cavity at five timestamps. Results: The presence of each herpesvirus in the oral cavity was observed in 3.2%, 12.9%, 19.3%, 32.2%, 54.8% and 93.5% patients for human herpesvirus (HHV)‐6A, herpes simplex virus‐1, HHV‐6B, cytomegalovirus (CMV), Epstein–Barr virus (EBV) and HHV‐7, respectively. Oral shedding of herpes virus was not uncommon after alloHSCT. There was a statistically significant association between the EBV and CMV oral shedding at C1 and the cumulative incidence of acute graft‐versus‐host disease (aGVHD). The results suggested that the presence of HSV‐1 at C2 was related to a relapse. The HHV‐7 oral shedding at C2 suggests a possible link between relapse, progression‐free survival and overall survival of the patients. Conclusions: Patients who developed aGVHD showed higher CMV and EBV shedding in the oral cavity at aplasia, suggesting modifications to the pattern of immune cell response and inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

microRNAs are a class of small, single-stranded, noncoding RNAs that regulate gene expression. They can be significantly dysregulated upon exposure to any infection, serving as important biomarkers and therapeutic targets. Numerous human DNA viruses, along with several herpesviruses, have been found to encode and express functional viral microRNAs known as vmiRNAs, which can play a vital role in host–pathogen interactions by controlling the viral life cycle and altering host biological pathways. Viruses have also adopted a variety of strategies to prevent being targeted by cellular miRNAs. Cellular miRNAs can act as anti- or proviral components, and their dysregulation occurs during a wide range of infections, including herpesvirus infection. This demonstrates the significance of miRNAs in host herpesvirus infection. The current state of knowledge regarding microRNAs and their role in the different stages of herpes virus infection are discussed in this review. It also delineates the therapeutic and biomarker potential of these microRNAs in future research directions. [ABSTRACT FROM AUTHOR]

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Herpesviruses are large DNA viruses that have long been used as powerful gene therapy tools. In recent years, the ability of herpesviruses to stimulate both innate and adaptive immune responses has led to their transition to various applications as vaccine vectors. This vaccinology branch is growing at an unprecedented and accelerated rate. To date, human herpesvirus-based vectors have been used in vaccines to combat a variety of infectious agents, including the Ebola virus, foot and mouth disease virus, and human immunodeficiency viruses. Additionally, these vectors are being tested as potential vaccines for cancer-associated antigens. Thanks to advances in recombinant DNA technology, immunology, and genomics, numerous steps in vaccine development have been greatly improved. A better understanding of herpesvirus biology and the interactions between these viruses and the host cells will undoubtedly foster the use of herpesvirus-based vaccine vectors in clinical settings. To overcome the existing drawbacks of these vectors, ongoing research is needed to further advance our knowledge of herpesvirus biology and to develop safer and more effective vaccine vectors. Advanced molecular virology and cell biology techniques must be used to better understand the mechanisms by which herpesviruses manipulate host cells and how viral gene expression is regulated during infection. In this review, we cover the underlying molecular structure of herpesviruses and the strategies used to engineer their genomes to optimize capacity and efficacy as vaccine vectors. Also, we assess the available data on the successful application of herpesvirus-based vaccines for combating diseases such as viral infections and the potential drawbacks and alternative approaches to surmount them.

Aves polyomavirus 1, psittacine beak and feather disease virus, and psittacid herpesvirus 1 are important pathogens of psittacine birds with the potential to cause substantial morbidity and mortality. Using publically available nucleotide sequences, we developed and validated a triplex real-time PCR (rtPCR) assay to rapidly detect these 3 viruses. The assay had high analytical sensitivity, detecting

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of unknown origin. The current paradigm is that disease develops in genetically susceptible individuals, influenced by environmental factors. Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have particularly strong associations with the disease. Both viruses are typically acquired during childhood, decades before MS presents. However, in patients with pediatric MS, the temporal window between viral acquisition and disease onset is shortened, which may provide insights into the association of herpesviruses with MS. OBJECTIVE: To compare the frequency of EBV and HHV-6 in the saliva of a cohort of pediatric MS patients and age-matched controls. METHODS: The study enrolled 32 pediatric MS patients and 42 controls and evaluated saliva for HHV-6 u57 and EBV lmp-1 amplification by droplet digital polymerase chain reaction (ddPCR). RESULTS: Pediatric MS patients did not differ from controls in the frequency or magnitude of salivary viral shedding. During the assessment of EBV positivity, distinct profiles emerged that correlated with target amplicon mutations. CONCLUSIONS: None of these mutations were evident in EBV-positive samples from pediatric MS patients, whereas they were present in pediatric controls, in addition to MS and control adults, suggesting differential host-immune control of EBV in this pediatric MS cohort.

We developed a computational approach called Domain-architecture Aware Inference of Orthologs (DAIO) for the analysis of protein orthology by combining phylogenetic and protein domain-architecture information. Using DAIO, we performed a systematic study of the proteomes of all human Herpesviridae species to define Strict Ortholog Groups (SOGs). In addition to assessing the taxonomic distribution for each protein based on sequence similarity, we performed a protein domain-architecture analysis for every protein family and computationally inferred gene duplication events. While many herpesvirus proteins have evolved without any detectable gene duplications or domain rearrangements, numerous herpesvirus protein families do exhibit complex evolutionary histories. Some proteins acquired additional domains (e.g., DNA polymerase), whereas others show a combination of domain acquisition and gene duplication (e.g., betaherpesvirus US22 family), with possible functional implications. This novel classification system of SOGs for human Herpesviridae proteins is available through the Virus Pathogen Resource (ViPR, www.viprbrc.org).

PurposeTo assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1).MethodsSubconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation.ResultsBoth groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable.ConclusionsSubconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is considered to be associated with post-viral complications and mental stress, but the role of autoimmunity also remains promising. A comparison of autoimmune profiles in chronic fatigue of different origin may bring insights on the pathogenesis of this disease. Thirty-three patients with CFS/ME were divided into three subgroups. The first group included Herpesviridae carriers (group V), the second group included stress-related causes of chronic fatigue (distress, group D), and the third group included idiopathic CFS/ME (group I). Were evaluated thirty-six neural and visceral autoantigens with the ELISA ELI-test (Biomarker, Russia) and compared to 20 healthy donors, either without any fatigue (group H), or “healthy but tired” (group HTd) with episodes of fatigue related to job burnout not fitting the CFS/ME criteria. β2-glycoprotein-I autoantibodies were increased in CFS/ME patients, but not in healthy participants, that alludes the link between CFS/ME and antiphospholipid syndrome (APS) earlier suspected by Berg et al. (1999). In CFS/ME patients, an increase in levels of autoantibodies towards the non-specific components of tissue debris (double-stranded DNA, collagen) was shown. Both CFS and HTd subgroups had elevated level of autoantibodies against serotonin receptors, glial fibrillary acidic protein and protein S100. Only group V showed an elevation in the autoantibodies towards voltage-gated calcium channels, and only group D had elevated levels of dopamine-, glutamate- and GABA-receptor autoantibodies, as well as NF200-protein autoantibodies. Therefore, increased autoimmune reactions to the multiple neural antigens and to adrenal medullar antigen, but not to other tissue-specific somatic ones were revealed. An increase in autoantibody levels towards some neural and non-tissue-specific antigens strongly correlated with a CFS/ME diagnosis. Autoimmune reactions were described in all subtypes of the clinically significant chronic fatigue. Visceral complaints in CFS/ME patients may be secondary to the neuroendocrine involvement and autoimmune dysautonomia. CFS may be closely interrelated with antiphospholipid syndrome, that requires further study.

Simple Summary: This study reports the pathology, molecular detection, isolation, and genetic characterization of a novel duck plague virus from a recent outbreak affecting domestic layer ducks in southern China, in December 2021. Our study emphasizes the urgent need to establish comprehensive and nationwide surveillance of DPV among poultry. Duck plague (DP) is a highly contagious viral disease in ducks caused by the duck plague virus (DPV). The DPV, a member of Herpesviridae, poses a severe threat to the waterfowl farming industry worldwide. In this study, we reported a recent outbreak of DPV in domestic laying ducks at 310 days of age from southern China in December 2021. The gross lesion, histopathologic examination, molecular detection, and genetic characterization studies of DPV are described here. As a result, gross lesions such as an enlarged congestive spleen and liver were observed. Liver with vacuolar degeneration and small vacuoles and spleen with hemosiderosis were remarkable microscopic findings. Our results suggested that the liver had the highest viral load, followed by the trachea, pancreas, kidney, brain, spleen, and heart. In addition, DPV was successfully isolated in chicken embryo fibroblast cell culture and designated as DP-GD-305-21. The UL2, UL12, UL41, UL47, and LORF11 genes of DP-GD-305-21 shared a high nucleotide homology with the Chinese virulent (CHv) strain and the Chinese variant (CV) strain. In conclusion, this study reports the isolation and molecular characterization of DPV from a recent outbreak in southern China. Our results contributed to the understanding of the pathological and molecular characterization of currently circulating DPV in China. [ABSTRACT FROM AUTHOR]

The family Herpesviridae includes viruses identified in mammals, birds and reptiles. All herpesviruses share a similar structure, consisting of a large linear double-stranded DNA genome surrounded by a proteic icosahedral capsid further contained within a lipidic bilayer envelope. The continuous rise of genetic variability and the evolutionary selective pressure underlie the appearance and consolidation of novel viral strains. This applies also to several gamma(γ)-herpesviruses, whose role as primary pathogen has been often neglected and, among these to newly emerged viruses or virus variants responsible for the development of Malignant Catarrhal Fever (MCF) or MCF-like disease. The identification of γ-herpesviruses adapted to new zoological hosts requires specific molecular tools for detection and characterization. These viruses can cause MCF in livestock and wild animals, a disease generally sporadic but with serious welfare implications and which, in many cases, leads to death within a few days from the appearance of the clinical signs. In the absence of a vaccine, the first step to improve disease control is based on the improvement of molecular tools to identify and characterize these viruses, their phylogenetic relationships and evolutionary interaction with the host species. A Panherpes PCR-specific test, based on the conserved DNA polymerase gene, employing consensus/degenerate and deoxyinosine-substituted primers followed by sequencing, is still the preferred diagnostic test to confirm and characterize herpesviral infections. The drawback of this test is the amplification of a relatively short sequence, which makes phylogenetic analysis less stringent. Based on these diagnostic requirements, and with a specific focus on γ-herpesviruses, the present review aims to critically analyze the currently available methods to identify and characterize novel MCFV strains, to highlight advantages and drawbacks and to identify the gaps to be filled in order to address research priorities. Possible approaches for improving or further developing these molecular tools are also suggested. [ABSTRACT FROM AUTHOR]

A molecular survey of herpesviruses in Australian native mammals was conducted, spanning 260 individuals from 27 species. Among the herpesviruses detected, a putative new gammaherpesvirus species was detected in the yellow‐bellied glider (Petaurus australis), and another in the critically endangered Leadbeater's possum (Gymnobelideus leadbeateri). In addition, the known host range of the putative species macropodid gammaherpesvirus 3 (MaHV‐3) is herein extended to the western grey kangaroo (Macropus fuliginosus). These findings expand our understanding of herpesviruses in Australian mammals and may inform biosecurity protocols for captive and translocated populations. [ABSTRACT FROM AUTHOR]

Introduction: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. Case report: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. Management & Outcome: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event. [ABSTRACT FROM AUTHOR]

The CRISPR/Cas9 system has been applied in the genome editing and disruption of latent infections for herpesviruses such as the herpes simplex virus, Epstein⁻Barr virus, cytomegalovirus, and Kaposi's sarcoma-associated herpesvirus. CRISPR/Cas9-directed mutagenesis can introduce similar types of mutations to the viral genome as can bacterial artificial chromosome recombination engineering, which maintains and reconstitutes the viral genome successfully. The cleavage mediated by CRISPR/Cas9 enables the manipulation of disease-associated viral strains with unprecedented efficiency and precision. Additionally, current therapies for herpesvirus productive and latent infections are limited in efficacy and cannot eradicate viruses. CRISPR/Cas9 is potentially adapted for antiviral treatment by specifically targeting viral genomes during latent infections. This review, which focuses on recently published progress, suggests that the CRISPR/Cas9 system is not only a useful tool for basic virology research, but also a promising strategy for the control and prevention of herpesvirus latent infections.

It has been reported that some specific changes in DNA methylation can be due to aging or infection by tumor-related viruses but the effect of herpes simplex virus type 1 (HSV-1) in this regard is unknown. HSV-1 is a well-known virus that causes cold sores. After the primary infection, the virus switches to latent infection and remains in the body for the whole life. As the location of DNA methylation, we focused on the promoter region of the COASY gene, which codes for coenzyme A synthase, because methylation in this region is reportedly associated with Alzheimer's disease (AD). During HSV-1 lytic infection, compared to non-infected cells, COASY DNA methylation decreased but when HSV-1 replication was inhibited by acyclovir, an anti-herpes agent, COASY DNA methylation increased. In addition, for expression of immediate early protein only, there was no significant change in COASY DNA methylation, while for expression of the capsid protein VP26, a late protein known to bind with DNA methyltransferase DNMT3A, in the nucleus only, COASY DNA methylation significantly increased compared to the control, without changes in DNMT3A mRNA. Our results suggested that DNA methylation occurred not due to transcriptional changes in DNMT3A but through translational regulation. In this research, we showed that host COASY DNA methylation is altered by HSV-1 infection, in particular by HSV-1 VP26. It is a potential cause of various diseases, and this is particularly relevant for AD.

Neuroinflammation is defined as an inflammatory state within the central nervous system (CNS). Microglia conprise the resident tissue macrophages of the neuronal tissue. Upon viral infection of the CNS, microglia become activated and start to produce inflammatory mediators important for clearance of the virus, but an excessive neuroinflammation can harm nearby neuronal cells. Herpesviruses express several molecular mechanisms, which can modulate apoptosis of infected neurons, astrocytes and microglia but also divert immune response initiated by the infected cells. In this review we also describe the link between virus-related neuroinflammation, and development of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Equine herpesvirus 1 (EHV-1) causes respiratory illness, fetal loss, perinatal mortality, and myeloencephalopathy. This study investigated ORF15's impact on virus infectivity and neurovirulence. The Ab4p neurovirulent strain of EHV1 was used as a backbone to create Ab4p attB, Ab4p∆ORF15, and Ab4p∆ORF15R chimeras via BAC DNA transfection into RK-13 cells. Viral growth kinetics, plaque size, transcription, and growth were assessed in MDBK cells, mouse neurons, and fetal equine brain cells. Neurovirulence was evaluated post-intranasal inoculation into male CBA/N1 SPF mice, measuring signs, virus titers, and histopathological changes. Deletion of EUL45 (Ab4p-∆EUL45) reduced viral replication efficiency, resulting in decreased release and smaller plaques. EUL45 deletion also upregulated neighbouring genes (EUL46 and EUL44). Ab4p-∆EUL45 exhibited reduced virulence and poor growth in neural cells compared to wild-type viruses. This study sheds light on EUL45's role in EHV-1, viral replication, and regulation of EUL46 and EUL44 expression, suggesting potential as a vaccine candidate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is considered to be associated with post-viral complications and mental stress, but the role of autoimmunity also remains promising. A comparison of autoimmune profiles in chronic fatigue of different origin may bring insights on the pathogenesis of this disease. Thirty-three patients with CFS/ME were divided into three subgroups. The first group included Herpesviridae carriers (group V), the second group included stress-related causes of chronic fatigue (distress, group D), and the third group included idiopathic CFS/ME (group I). Were evaluated thirty-six neural and visceral autoantigens with the ELISA ELI-test (Biomarker, Russia) and compared to 20 healthy donors, either without any fatigue (group H), or "healthy but tired" (group HTd) with episodes of fatigue related to job burnout not fitting the CFS/ME criteria. β2-glycoprotein-I autoantibodies were increased in CFS/ME patients, but not in healthy participants, that alludes the link between CFS/ME and antiphospholipid syndrome (APS) earlier suspected by Berg et al. (1999). In CFS/ME patients, an increase in levels of autoantibodies towards the non-specific components of tissue debris (double-stranded DNA, collagen) was shown. Both CFS and HTd subgroups had elevated level of autoantibodies against serotonin receptors, glial fibrillary acidic protein and protein S100. Only group V showed an elevation in the autoantibodies towards voltage-gated calcium channels, and only group D had elevated levels of dopamine-, glutamate- and GABA-receptor autoantibodies, as well as NF200-protein autoantibodies. Therefore, increased autoimmune reactions to the multiple neural antigens and to adrenal medullar antigen, but not to other tissue-specific somatic ones were revealed. An increase in autoantibody levels towards some neural and non-tissue-specific antigens strongly correlated with a CFS/ME diagnosis. Autoimmune reactions were described in all subtypes of the clinically significant chronic fatigue. Visceral complaints in CFS/ME patients may be secondary to the neuroendocrine involvement and autoimmune dysautonomia. CFS may be closely interrelated with antiphospholipid syndrome, that requires further study. [ABSTRACT FROM AUTHOR]