Herpes Simplex Virus Research Articles

HSV-1 Infection Alters MAPT Splicing and Promotes Tau Pathology in Neural Models of Alzheimer's Disease.

Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's Disease (AD) in neurons. One key marker of AD is the hyperphosphorylation of Tau, accompanied by altered levels of Tau isoforms. However, an imbalance in these Tau splice variants, specifically resulting from altered 3R to 4R MAPT splicing of exon 10, has yet to be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models with HSV-1 and monitored MAPT splicing and Tau phosphorylation. Further, we transduced SH-SY5Y-neurons with HSV-1 ICP27 which alters RNA splicing to analyze if ICP27 alone is sufficient to induce altered MAPT exon 10 splicing. We show that HSV-1 infection induces altered splicing of MAPT exon 10, increasing 4R-Tau protein levels, Tau hyperphosphorylation, and Tau oligomerization. Our experiments reveal a novel link between HSV-1 infection and the development of cytopathic phenotypes linked with AD progression. HSV-1 infection in forebrain organoids reduces the neurite length of MAP2-positive neurons.HSV-1 infection increases Tau hyperphosphorylation in both two-month-old and four-month-old forebrain organoids. HSV-1 infection increases Exon 10 containing (4R) MAPT mRNA and 4R-Tau protein expression in both forebrain organoids and human SH-SY5Y-neurons. HSV-1 ICP27 is both necessary and sufficient to induce increased 4R MAPT mRNA and 4R-Tau protein expression in SH-SY5Y-neurons. HSV-1 infection increases Tau oligomerization in both forebrain organoids and SH-SY5Y-neurons.

Lactylation of RNA m6A demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus

RNA N6-methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) plays a crucial role in regulating innate immunity. Lysine acylation, a widespread protein modification, influences protein function, but its impact on ALKBH5 during viral infections has not been well characterized. This study investigates the presence and regulatory mechanisms of a previously unidentified lysine acylation in ALKBH5 and its role in mediating m6A modifications to activate antiviral innate immune responses. We demonstrate that ALKBH5 undergoes lactylation, which is essential for an effective innate immune response against DNA herpesviruses, including herpes simplex virus type 1 (HSV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), and mpox virus (MPXV). This lactylation attenuates viral replication. Mechanistically, viral infections enhance ALKBH5 lactylation by increasing its interaction with acetyltransferase ESCO2 and decreasing its interaction with deacetyltransferase SIRT6. Lactylated ALKBH5 binds interferon-beta (IFN-β) messenger RNA (mRNA), leading to demethylation of its m6A modifications and promoting IFN-β mRNA biogenesis. Overexpression of ESCO2 or depletion of SIRT6 further enhances ALKBH5 lactylation to strengthen IFN-β mRNA biogenesis. Our results identify a posttranslational modification of ALKBH5 and its role in regulating antiviral innate immune responses through m6A modification. The finding provides an understanding of innate immunity and offers a potential therapeutic target for HSV-1, KSHV, and MPXV infections.

Seroprevalence of herpes simplex virus 2 infection among commercial sex workers in Colombo, Sri Lanka

Background: Herpes Simplex Virus Type 2 (HSV2) causes genital herpes, an incurable, lifelong sexually transmitted infection (STI). This study was conducted to describe the seroprevalence and associated factors of HSV2 infection in a cohort of Female Sex Workers (FSWs). Methods: A descriptive cross-sectional study was conducted on 136 FSWs who attended the central STD Clinic, in Colombo. They were assessed using an interviewer-administered questionnaire followed by serum sampling. Serum samples were tested for HSV2 IgG using an enzyme immunoassay specific for glycoprotein gG2 of HSV2. Results: HSV2 seroprevalence of FSW was 66.9% (91/136) of which only 14.3% (13/91) reported a history of genital infection. Age ≥35 years (OR 3.35, 95%CI 1.54-7.31, p=0.002), education ≥ grade 5 (OR 8.35, 95%CI 13.1- 64.7, p<0.001), lifetime sexual partners ≥ 200 (OR 5.33, 95% CI 2.3-12.36), p<0.001), duration of sex work ≥1 year (OR 4.5, 95% CI 2.09-9.65, p<0.001) and history of STI (OR 4.52, 95% CI 1.9-10.78, p<0.001) were statistically significant risk factors for high HSV2 prevalence. Consistent condom use by commercial partners in the last 3 months was not a significant protective factor in preventing HSV2 infection (OR 0.44, 95% CI 0.15-1.26, p = 0.12) in this cohort. Conclusions: The seroprevalence of HSV2 is high in this population and most of them did not report any genital infection. Multiple risk factors for higher prevalence were observed. Findings support the need for regular surveillance, monitoring of HSV-2 infection in high-risk populations, and expanding awareness of HSV-2 infection in the country.

Retraction: Cytomegalovirus and Herpes Simplex Virus Effect on the Prognosis of Mechanically Ventilated Patients Suspected to Have Ventilator-Associated Pneumonia.

Retraction: Cytomegalovirus and Herpes Simplex Virus Effect on the Prognosis of Mechanically Ventilated Patients Suspected to Have Ventilator-Associated Pneumonia.

Diagnostic yield of stains for infectious organisms in esophageal or gastroesophageal junction biopsies with esophagitis*

ABSTRACT Stains frequently performed to exclude infectious etiologies in esophagitis include Grocott methenamine silver (GMS) and periodic acid–Schiff (PAS) as well as immunohistochemistry (IHC) assays for cytomegalovirus (CMV) and herpes simplex virus (HSV). The diagnostic yield of these tests, in this situation, has not been well studied. We retrospectively reviewed 261 esophageal biopsies, which had one or more of the above tests performed. The diagnostic yield for GMS and PAS was 8%, while CMV and HSV immunohistochemistry had a diagnostic yield of 1% and 0%, respectively. Our study suggests that routine use of ancillary labeling techniques in esophagitis biopsies may be of limited utility and have low diagnostic yield.

Epidemiology and treatment of herpes simplex virus in the neonatal intensive care unit.

Describe the epidemiology and clinical characteristics of infants in the neonatal intensive care unit (NICU) with acyclovir exposure and herpes simplex virus (HSV) infection. Our primary analysis was to evaluate the prevalence of HSV infection among infants in the NICU who received acyclovir. We compared characteristics of infants with and without HSV and used multivariable regression analyses to assess associations between infection and clinical outcomes. Of 1,057,061 infants, 17,910 (2%) received acyclovir. Of those who received acyclovir, 1090 (5%) had HSV. Infection was associated with lower gestational age and lower birth weight. Multivariable models demonstrated that infected infants had higher mortality, greater postmenstrual age at discharge, and longer length of stay. Infants in the NICU who received acyclovir and have HSV are more likely to be born at lower gestational age, have lower birth weight, and have higher morbidities and mortality.

Microbiological bases of obsessive‑compulsive disorder - the role of viruses, bacteria, and parasites in the onset and progression of OCD.

Obsessive‑compulsive disorder (OCD) is a current topic of discussion nowadays. OCD presents a variety of different etiologies including environmental, viral, cognitive, or genetic aspects. In this article, we focused on the possible correlation between various infectious diseases as well as generally the relationship between viruses, bacteria, and parasites, and an increased OCD risk. In this narrative review, we analyzed different types of articles found on PubMed, Google Scholar, and Scopus, as well as the articles of the National Institute of Mental Health. Searching criteria included articles from 1991 till the end of November, research involving human and animal patients (including monkeys and rats), and research published in English. Research showed a relationship between Herpes simplex virus, Rubella virus, Human immunodeficiency virus, Borna disease virus, Mycoplasma pneumoniae, Toxoplasma gondii, streptococcal infections, as well as gut microbiota and increased OCD risk. The possible mechanisms of this relation include neuroinflammation, brain tissue damage, autoimmune processes, and impairments in neurotransmitter levels. Infections caused by Varicella zoster virus, Measles virus, Mumps virus, Epstein‑Barr virus, Cytomegalovirus, or Borrelia Burgdorferi may also contribute to the increased risk of OCD. Reports showed an increased frequency of OCD occurrence in a group of infected people compared to a healthy group. However, there is no evidence of the influence of Influenza virus, Coxsackie virus, Poliovirus, Parvovirus B19, Enterovirus 71, West Nile virus, Treponema Pallidum, or Toxocara infections on the OCD risk. There is a significant relationship between various infectious diseases and an increased OCD risk. However, further studies are crucial to discover the exact pathomechanisms of these correlations and the potential influence of other pathogens on the onset of OCD.

Herpes Simplex Virus Type 2 Blocks IFN-β Production through the Viral UL24 N-Terminal Domain-Mediated Inhibition of IRF-3 Phosphorylation.

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

Improved antitumor effectiveness of oncolytic HSV-1 viruses engineered with IL-15/IL-15Rα complex combined with oncolytic HSV-1-aPD1 targets colon cancer

Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

Prompt diagnosis and treatment of peri-orbital necrotising fasciitis caused by group A β-haemolytic Streptococcus (GAS): a case report.

Necrotising fasciitis is a devastating infection characterised by rapidly progressing necrotising infection of the superficial fascia with secondary necrosis of the overlying skin. To describe the pathophysiology, differential diagnosis, and outcome in a rare case of periorbital necrotising fasciitis caused by group A β-haemolytic Streptococcus. A 60-year-old female with insulin-dependent diabetes presented with pyrexia and bilateral peri-orbital swelling, progressing to left periorbital necrotising fasciitis. It was caused by dual infection with group A β-haemolytic Streptococcus and Herpes Simplex Virus 1. A combination of intravenous antibiotics and surgical debridement and subsequent skin grafting resulted in a beneficial outcome in our patient. Differentiating cellulitis and necrotising fasciitis can be difficult when presenting signs and symptoms are non-specific. If not treated quickly with antibiotics and debridement of the infected tissue, the patient may develop septic shock within hours.

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism. Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis. The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment. We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

Etiology, Clinical Profiles, and Outcomes of Acute Encephalitis Syndrome Cases Admitted to a Tertiary Care Center in Myanmar in 2023.

The diagnosis of encephalitis is a challenging problem due to the heterogeneity of clinical presentations. The objective was to determine the etiology, clinical features, laboratory parameters, radiological findings, and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. A prospective descriptive study was conducted at the Neuromedical Ward of Yangon General Hospital from March to August 2023. Eighty-one AES cases were enrolled, and cerebrospinal fluid (CSF) samples were collected. A Qiastat ME Panel was used to detect viral, bacterial, and fungal pathogens. Seventeen out of eighty-one (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 encephalitis cases, the exact infectious and immune etiologies were identified in 31 of 64 cases (48.4%); 26 of these (83.9%) were due to infectious causes and 5 (16.1%) were immune encephalitis. Among the infectious causes, six Herpes Simplex Virus-1-, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis-, three Haemophilus influenzae-, two Streptococcus pneumoniae-, one Streptococcus pyogenes-, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with meningoencephalitis)-, and two Cryptococcus neoformans-infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis, and Aspergillus were identified. One case was a dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (p < 0.05). In total, 6.45% (2/31) of encephalitis patients with identified causes and 12.12% (4/33) of those without an identified organism had poor outcome. Herpes encephalitis and tuberculous meningoencepalitis were the commonest. This study highlighted that molecular testing with a multidisciplinary approach is required to ensure the right treatment on time.

Demographic, Behavioural, and Biological Factors Seen in Men Who Have Sex with Men with Salmonella spp.: A Systematic Review

Background: The sexual transmissibility of enteric pathogens, including Salmonella spp., has been described in men who have sex with men (MSM). However, the factors seen in MSM with Salmonella spp. are poorly understood. Method: We aimed to systematically review the literature to explore any factors seen in MSM with Salmonella spp. (MSM). We searched six databases—Medline, PubMed, CINAHL, Embase, Emcare, and Global Health—in April 2024 for manuscripts which contained primary peer-reviewed data in English and the measurement of any risk factors observed in MSM with Salmonella spp. This review was registered on PROSPERO (CRD42023472864). Results: Eleven manuscripts were included in the final review and highlighted demographic (living with HIV), behavioural (oral–anal sex, receptive and penetrative anal sex, hand licking to stimulate their partner, group sex, non-condom use), and biological (co-infection with CMV, Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, Shigella spp.; previous infection with Treponema pallidum, Neisseria gonorhoeae, Chlamydia trachomatis and hepatitis B; and antimicrobial treatment failure) factors seen in MSM with Salmonella spp. Conclusion: Despite a limited number of manuscripts and individuals, this review highlighted some potential demographic, behavioural, and biological factors implicated in the transmission of Salmonella spp. in MSM. These data will provide insights for future guidelines, public health control strategies, and research.

A fur plucking model to study herpes simplex virus reactivation and recurrent disease.

Herpes simplex viruses (HSV-1 and HSV-2) have infected over half of the US adult population to cause a lifelong, persistent infection; however, our understanding of the mechanisms that govern HSV reactivation and recurrent disease is incomplete. This is in part due to limitations in the animal models used to study recurrent disease, which are laborious and inefficient in mice. To address this technical gap, we developed a mouse model in which fur plucking after flank skin infection is sufficient to induce episodes of HSV reactivation and recurrent disease. Our work provides a model for the field to investigate the pathogenic mechanisms of HSV and immune responses during recurrent disease and provides an opportunity to investigate the neurobiology of HSV infection.

Virus-Induced Voracity: Uncovering Hyperphagia Post-Herpes Simplex Virus Type 1.

Herpes simplex virus type 1 (HSV-1) is the leading cause of sporadic fatal encephalitis, typically presenting with temporal lobe abnormalities. It usually manifests as fever, headache, seizure, altered sensorium, and focal neurological deficit. Hyperphagia as a sole complication of HSV-1 encephalitis is a rare presentation. We report a 25-year-old woman with a 10-day history of fever, headache, and vomiting, progressing to confusion, visual hallucinations, and drowsiness. She had a history of meningoencephalitis at age 8 and well-controlled focal seizures. Upon admission, magnetic resonance imaging showed T2/fluid-attenuated inversion recovery hyperintensities in both temporal lobes with diffusion restriction. Electroencephalography indicated generalized slowing and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis with elevated protein levels. Viral encephalitis was suspected, and intravenous acyclovir was initiated. CSF polymerase chain reaction (PCR) confirmed HSV-1. With treatment, she gradually improved but developed hyperphagia during hospital stay. Hyperphagia, a rare complication of herpes simplex virus (HSV) encephalitis, is a part of Kluver-Bucy syndrome typically associated with other cognitive dysfunctions. Despite early treatment, voracious appetite remained partially, emphasizing the need for rapid diagnosis and treatment to prevent severe outcomes. The case highlights that acute onset hyperphagia can be an isolated complication of HSV encephalitis, requiring tailored therapeutic strategies. Follow-up showed significant weight gain with partial improvement in hyperphagia, underscoring the challenges in managing this condition.

The alphaherpesvirus gE/gI glycoprotein complex and proteases jointly orchestrate invasion across the host's upper respiratory epithelial barrier.

Herpes simplex virus type 1 (HSV-1) infections are a worldwide issue. More than three billion people are infected with HSV-1 globally. Although most infections with HSV-1 occur subclinically, severe symptoms and complications are numerous and can be life-threatening. Complications include encephalitis and blindness. Recently, HSV-1 infections have been associated with the development of Alzheimer's Disease. To date, no effective vaccines against HSV-1 are on the market. Pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1) are two alphaherpesviruses of major veterinary importance. Although efforts have been made to eradicate these viruses from livestock animals, clinical problems still occur, resulting in great economic losses for farmers. It is evident that new insights into the pathogenesis of alphaherpesviruses are needed, to develop effective treatments and novel preventive therapies.

Association between human herpes simplex virus and severe headache or migraine among aged 20-49 years: a cross-sectional study.

Previous studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine. The cross-sectional data on 5,730 participants aged 20-49 years were obtained from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses. Our study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03-1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (-) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04-1.91, p = 0.0281). HSV-2 gG-2(+) was significantly associated with severe headache or migraine.

Co-infection of human papillomavirus and herpes simplex virus-2 with cervical dysplasia among women in Kaduna State, Nigeria

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

Herpesvirus Antibody Response and Occurrence of Symptoms in Acute and Post-Acute COVID-19 Disease.

Knowledge about the underlying causes of the individual occurrence of symptoms during acute COVID-19 disease and during the post-acute sequelae of COVID-19 is limited. In a German COVID-19 follow-up study, we assessed whether elevated antibody responses to herpesviruses were associated with symptom occurrence in acute COVID-19 disease (n = 96 participants) and during 20 months of follow-up (n = 62 participants). Serum samples were analyzed for their antibodies to herpes simplex virus (HSV)-1 and -2, Epstein-Barr virus (EBV), and Cytomegalovirus (CMV) using fluorescent bead-based multiplex serology. The association of herpesvirus antibodies with symptom occurrence (fatigue, fever, dyspnea, decrease in taste, concentration problems) was assessed using multivariate logistic regression models. High EBV antibody levels were significantly associated with a more than fourfold increased odds of experiencing fatigue during acute COVID-19 disease and during follow-up. High CMV antibody levels were significantly associated with a more than threefold increased odds of experiencing concentration problems and a decrease in taste during the follow-up. The HSV-1 and -2 antibody levels were not elevated in the individuals that experienced symptoms. In conclusion, our findings indicate that herpesvirus infections, specifically EBV and CMV infections, might play a role in symptom development during acute and post-acute COVID-19 disease. It remains to be elucidated whether the elevated EBV and CMV antibodies determined in our study are indicators of herpesvirus reactivation.

Sulfated xylogalactofucans from Spatoglossum asperum: Production, structural features and antiviral activity

In cultured cells, herpes simplex virus (HSV) infectivity is successfully inhibited by sulfated polysaccharides. Herein, we utilized an amalgamated extraction-sulfation procedure to produce two xylogalactofucan sulfates (S203 and S204) from Spatoglossum asperum using ClSO3H.Pyr/DMF and SO3.Pyr/DMF reagents, respectively. Among these xylogalactofucans, the 17 ± 12 kDa polymer (S203) with 14 % sulfate exhibited activity on several HSV variants, including an acyclovir-resistant HSV-1 strain. This is the first report of the anti-HSV activity of a sulfated xylogalactofucan of S. asperum. The effective concentration 50 % (EC50) value of S203 against HSV-1 strain F was 0.6 μg/mL with a selectivity index of 833. The backbone of this polymer (S203) is made up mostly of (1 → 4)-linked-α-l-Fucp units having sulfate groups typically at O–3 and sometimes at O–2 positions. Oligosaccharides containing Xyl, Gal and Fuc units confirms that they are an integral part of a single polymer, another novelty of this study.The EC50 values of the native xylogalactofucan (S202) and the SO3.Pyr/DMF modified polymer (S204), containing 2 % and 6 % sulfates, were >100 and 3.3 μg/mL, respectively. Introduction of sulfate groups enhanced their capability to inhibit the infection of cells by HSV-1. These findings suggest feasibility of inhibiting HSV attachment to cells by blocking viral entry with polysaccharide having specific structure.