Disparities in burden of herpes simplex virus type 2 in China: systematic review, meta-analyses, and meta-regressions.

Background: The rising prevalence of herpes simplex type 2 (HSV-2) infection poses a growing global public health challenge. A comprehensive understanding of its epidemiology and burden disparities in China is crucial for informing targeted and effective intervention strategies in the future. Methods: We followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 31st, 2024. We synthesized HSV-2 seroprevalence data across different population types. We used random-effects models for meta-analyses and conducted meta-regression to assess the association between population characteristics and seroprevalence. Results: Overall, 23,999 articles were identified, and 402 publications (1,203,362 participants) that reported the overall seroprevalence rates (858 stratified measures) were included. Pooled HSV-2 seroprevalence among the general population (lower risk) was 7.7% (95% CI: 6.8-8.7%). Compared to the general population, there is a higher risk of HSV-2 prevalence among intermediate-risk populations (14.8%, 95% CI: 11.0-19.1%), and key populations (31.7%, 95% CI: 27.4-36.1%). Female sexual workers (FSWs) have the highest HSV-2 risk (ARR:1.69, 95% CI: 1.61-1.78). We found northeastern regions had a higher HSV-2 seroprevalence than other regions (17.0%, 95% CI: 4.3-35.6%, ARR: 1.38, 95% CI: 1.26-1.50, Northern China as the reference group). This highlighted the disparity by population risk levels and regions. We also found lower HSV-2 prevalence estimates in publications in Chinese bibliographic databases than those in English databases among key populations (such as MSM and HIV-discordant populations). Conclusion: There is a gradient increase in HSV-2 prevalence risk stratification. We also identified region, population, and age disparities and heterogeneities by publication language in the HSV-2 burden. This study provides guidance for future HSV-2 prevention to eliminate disparities of HSV-2 infection and reduce overall HSV-2 burden. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=408108, identifier CRD42023408108.

Targeting Peptidylarginine Deiminase 3 to Efficiently Suppress Herpes Simplex Virus Type 2 Infection.

Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 µM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

VP5 protein of oncolytic herpes simplex virus type 2 induces apoptosis in A549 cells through TP53I3 protein.

Oncolytic virotherapy stands out as a burgeoning and promising therapeutic paradigm, harnessing the intrinsic cytotoxicity of oncolytic viruses for selective replication and dissemination within tumors. The primary mode of action revolves around the direct eradication of tumor cells. In our previous investigations, we formulated an oncolytic herpes simplex virus type 2 (OH2) and substantiated its anti-tumor efficacy both in vivo and in vitro. Subsequently, we embarked on a phase I/II clinical trial in China (NMPA, 2018L02743) and the USA (FDA, IND 27137) to assess OH2's safety, biodistribution, and anti-tumor activity as a standalone agent in patients with advanced solid tumors. In this investigation, our primary focus was to comprehend the influence of the major capsid protein VP5 of OH2 on its efficacy as an antitumor agent. Our findings underscore that the VP5 protein significantly amplifies OH2's oncolytic impact on A549 cells. Additionally, we observed that VP5 actively promotes the induction of apoptosis in A549 cells, both in vivo and in vitro. Through comprehensive transcriptional sequencing, we further authenticated that the VP5 protein triggers apoptosis-related signaling pathways and Gene Ontology (GO) terms in A549 cells. Moreover, we scrutinized differentially expressed genes in the p53-dependent apoptosis pathway and conducted meticulous in vitro validation of these genes. Subsequently, we delved deeper into unraveling the functional significance of the TP53I3 gene and conclusively affirmed that the VP5 protein induces apoptosis in A549 cells through the TP53I3 gene. These revelations illuminate the underlying mechanisms of OH2's antitumor activity and underscore the pivotal role played by the VP5 protein. The outcomes of our study harbor promising implications for the formulation of effective oncolytic virotherapy strategies in cancer treatment.

Acute-Onset Lower Extremity Weakness and Urinary Retention in a Chronically Immunosuppressed Patient: Diagnosis and Management of Herpes Simplex Virus Type 2 Myelitis.

A 34-year-old immunosuppressed male presented with worsening bilateral lower extremity weakness and urinary retention accompanied by a painless clean-based chancre on his glans penis. Physical examination revealed symmetrically diminished lower extremity weakness most pronounced with hip flexion and knee extension and absent Achilles reflexes. Full MRI spine without contrast was noncontributory. Lumbar puncture showed elevated protein and total nucleated cells with lymphocytic predominance. Both CSF and serum polymerase chain reaction were positive for herpes simplex virus type 2. He received IV methylprednisolone and acyclovir and underwent four months of physical therapy with complete resolution of his neurologic deficits.

Incidence of herpes simplex virus type 2 positivity among women living with human immunodeficiency virus in South Africa.

BACKGROUND: For women living with HIV (WLHIV), co-infection with herpes simplex virus type 2 (HSV-2) causes severe genital ulcers and presents additional challenges for their HIV care. To inform preventive strategies, we aimed to determine the incidence and risk factors of HSV-2 positivity in a prospective cohort of South African women. METHODS: The CAPRISA 002 study enrolled women at acute HIV infection between 2004 and 2020. HSV-2 testing was conducted by multiplex polymerase chain reaction (PCR) assay on collected vaginal swabs up to twice annually during follow-up. We calculated incidence as the number of new cases per 100 person-years (PYs) and used Cox-proportional-hazard regression to identify factors associated with time-to-HSV-2 PCR positivity. RESULTS: At enrolment, the median age of 171 women was 24 years, interquartile range (IQR 21-28), and the estimated median days since HIV infection was 42 (IQR 22-65). Of participants tested at enrolment, HSV-2 antibody prevalence was 81.4% (105/129), and 10.6% (12/113) were positive by PCR. Among 147 women with a prior negative HSV-2 PCR diagnosis, we observed 47 new HSV-2 PCR positive cases over 424.4 PYs of follow-up, yielding an incidence rate of 11.1 cases per-100-PYs. HSV-2 PCR positivity incidence was higher among younger women (<25 years: adjusted Hazard Ratio [aHR] = 5.91, 95%CI 3.02-11.6), those with bacterial vaginosis (BV) (Nugent score 7-10: aHR = 2.17, 95%CI 1.15-4.10) and lower CD4 counts (<500 cells/µl: aHR = 2.04, 95%CI 1.08-3.87). CONCLUSION: After acute HIV infection in women, the incidence of HSV-2 PCR positivity was associated with younger age, BV diagnosis and lower CD4 count.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Antiviral activity of terpenes isolated from marine brown seaweeds against herpes simplex virus type 2.

Herpes simplex virus type 2 (HSV-2) is the most common agent of sexually transmitted infections around the world. Currently, no vaccine is available, and acyclovir is the reference compound in treatment HSV-2 infections. However, the emergence of resistant strains has reduced the efficacy in treatment. Several studies have shown marine seaweed biological activities, but there are no studies yet about the activity anti-HSV-2 of two its secundary metabolites, atomaric acid (1) and marine dolastane (2), isolated from Stypopodium zonale and Canistrocarpus cervicornis respectively. Therefore, we evaluated the anti-HSV-2 activity of compounds 1 and 2. Both compounds showed anti-HSV-2 activity with low cytotoxicity and compound 1 inactivated 90% of the viral particles at 50 µM. Both compounds inhibited the penetration and results in silico indicated the compound 1 as possible therapy alternative anti -HSV-2.

Immunogenicity and Therapeutic Efficacy of a Sendai-Virus-Vectored HSV-2 Vaccine in Mouse and Guinea Pig Models.

BACKGROUND: To date, there is no licensed vaccine for preventing herpes simplex virus type 2 (HSV-2). The current treatment to address the infection and prevent its transmission is not always satisfactory. METHODS: We constructed two recombinant vectors, one encoding HSV-2 glycoprotein D (gD, SeV-dF/HSV-2-gD) and one encoding HSV-2-infected cell protein 27 (ICP27, SeV-dF/HSV-2-ICP27), based on a replication-defective Sendai virus through reverse genetics, collectively comprising a combinatorial HSV-2 therapeutic vaccine candidate. The immunogenicity and proper immunization procedure for this vaccine were explored in a murine model. The therapeutic effect that helps prevent recurrent HSV-2 disease was evaluated in HSV-2-infected guinea pigs. RESULTS: Both a robust humoral immune response and a cellular immune response, characterized by the neutralizing antibody titer and the IFN-γ level, respectively, were elicited in BALB/c mice. A further study of cellular immunogenicity in mice revealed that T lymphocytes were successfully enhanced with the desirable secretion of several cytokines. In HSV-2-seropositive guinea pigs, vaccination could reduce the severity of HSV-2 in terms of recurrent lesions, duration of recurrent outbreak, and frequency of recurrence by 58.66%, 45.34%, and 45.09%, respectively, while viral shedding was also significantly inhibited in the vaccine-treated group compared to the group treated with phosphate-buffered saline. CONCLUSIONS: The replication-defective recombinant Sendai viruses conveying HSV-2-gD and ICP27 proteins showed great immunogenicity and potential for preventing recurrent HSV-2 disease.

The prevalence of varicella zoster virus, herpes simplex virus type 2, and human papillomavirus in breast cancerous tissues and their adjacent ones in Iran.

Background: Breast cancer is the second type of cancer in the world. Some internal and external risk factors, especially infection diseases, can progress breast cancer. As the relation between varicella zoster virus (VZV), human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), and breast cancer has not been understood, it was attempting to find the effect of these viruses and breast cancer in this study. Materials and Methods: We collected 40 breast cancer and 50 healthy adjacent tissues from Taleghani and Imam Hossein Hospital, Tehran, Iran, in 3 years starting in 2017. After extracting DNA from breast tissues, multiplex polymerase chain reaction (PCR), nested PCR, and PCR were done to analyze the prevalence of HSV-2, VZV, and HPV. Results: Our results showed that HPV may be one of the important causes of breast cancer. Nested PCR illustrated nine breast cancerous tissues (mean age: 43) and three healthy adjacent ones (mean age: 41) were infected by HPV. Phylogenetic analysis illustrated that all of the infected HPV cancerous and healthy tissues were HPV 18 (except two healthy samples infected with HPV 6). Nevertheless, there were not any infected tissues by HSV-2 and VZV. Conclusion: It seems that HPV virus type 18 can have high prevalence in breast cancerous tissues in comparison with healthy adjacent ones, and it is likely to have an effect on breast cancer progression. However, the opposite trend is true for HSV-2 and VZV as we did not find any differences between different kinds of breast tissues.

Severe acute herpes virus type 2 primo-infection and its association with anti-type 1 interferon autoantibodies.

Herpes simplex virus type 2 (HSV-2) is a common cause of infection, which is usually self-limited and asymptomatic. A 71-year-old patient with HSV-2 primo-infection developed acute hepatitis and secondary hemophagocytic lymphohistiocytosis. The patient had high levels of autoantibodies against type I interferon (IFN) (> 1000 ng/mL), neutralizing high concentration (10 ng/mL) of both IFN-α and IFN-ω but not IFN-ß. Anti-IFN-I auto-antibodies are rarely observed in healthy individuals; however, their prevalence increases in individuals over 70 years of age and have been identified as a cause of some severe viral diseases, including critical COVID-19. Considering the function of IFN-I in innate immunity, the pathological role of these autoantibodies in severe viral diseases following primo-infections in elderly patient appears crucial.

Preclinical safety assessment of an oncolytic herpes simplex virus type 2 expressed PD-L1/CD3 bispecific antibody.

Oncolytic virotherapy is an emerging and safe therapeutic approach based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus armed with Bispecific Antibody (BsAb) molecules targeting PD-L1/CD3 (oHSV2-PD-L1/CD3-BsAb) to treat human malignancies. We demonstrated the anti-tumor efficacy of oHSV2-PD-L1/CD3-BsAb. To move forward with clinical trials of oHSV2-PD-L1/CD3-BsAb, we conducted a comprehensive preclinical safety evaluation, including hemolysis test, anaphylaxis test, repeated dose toxicity test in cynomolgus monkeys, biodistribution in cynomolgus monkeys and tissue cross-reactivity of PD-L1/CD3-BsAb with human and cynomolgus monkey tissues in vitro. Our preclinical safety evaluation indicated that oHSV2-PD-L1/CD3-BsAb is safe and suitable for clinical trials. After undergoing a thorough evaluation by the United States Food and Drug Administration (FDA), oHSV2-PD-L1/CD3-BsAb has successfully obtained approval to initiate Phase I clinical trials in the United States (FDA IND: 28717).

Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection.

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Recurrent Genital Herpes Triggering Ulcerative Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that presents as painful, rapidly growing skin ulcers with undermined edges and a violaceous, ragged border at the periphery and is non-responsive to conventional treatments. The average onset age is in the fourth decade, with a female preponderance. Genital PG is uncommon and may present singly or coexist with common sexually transmitted genital ulcerative diseases, which causes delays in the diagnosis and treatment of genital PG, thereby adding to the morbidity. Here, we highlight a case of non-healing genital ulcers that did not respond to conventional antibiotic treatment and aggravated each month with menstruation. In this case, menstruation acted as a trigger factor for the development of a herpes genital infection. The latter acts as a pathergy for the monthly aggravation of genital PG. The patient responded to treatment with anti-viral medications and immunosuppressive medications.

Comparison of effects of multiple adjuvants and immunization routes on the immunogenicity and protection of HSV-2 gD subunit vaccine.

Genital herpes caused by herpes simplex virus type 2 (HSV-2) poses a global health issue. HSV-2 infection increases the risk of acquiring HIV infection. Studies have demonstrated that HSV-2 subunit vaccines have potential benefits, but require adjuvants to induce a balanced Th1/Th2 response. To develop a novel, effective vaccine, in this study, a truncated glycoprotein D (aa 1-285) of HSV-2 was formulated with an Al(OH)3 adjuvant, three squalene adjuvants, zMF59, zAS03, and zAS02, or a mucosal adjuvant, bacterium-like particles (BLPs). The immunogenicity of these subunit vaccines was evaluated in mice. After three immunizations, vaccines formulated with Al(OH)3, zMF59, zAS03, and zAS02 (intramuscularly) induced higher titers of neutralizing antibody than that formulated without adjuvant, and in particular, mice immunized with the vaccine plus zAS02 had the highest neutralizing antibody titers and tended to produce a more balanced immune reaction than others. Intranasal gD2-PA-BLPs also induced excellent IgA levels and a more balanced Th1 and Th2 responses than intranasal gD2. After challenge with a lethal dose of HSV-2, all five adjuvants exhibited a positive effect in improving the survival rate. zAS02 and gD2-PA-BLPs enhanced survival by 50% and 25%, respectively, when compared with the vaccine without adjuvant. zAS02 was the only adjuvant that resulted in complete vaginal virus clearance and genital lesion healing within eight days. These results demonstrate the potential of using zAS02 as a subunit vaccine adjuvant, and BLPs as a mucosal vaccine adjuvant.

Contribution of carbohydrate-related metabolism in Herpesvirus infections.

Human herpesviruses are enveloped viruses with double-stranded linear DNA genomes highly prevalent in the human population. These viruses are subdivided into three subfamilies, namely alphaherpesvirinae (herpes simplex virus type 1, HSV-1; herpes simplex virus type 2, HSV-2; and varicella-zoster virus, VZV), betaherpesvirinae (human cytomegalovirus, HCMV; human herpesvirus 6, HHV-6; and human herpesvirus 7, HHV-7) and gammaherpesvirinae (Epstein-Barr virus, EBV; and Kaposi's sarcoma-associated herpesvirus, KSHV). Besides encoding numerous molecular determinants to evade the host antiviral responses, these viruses also modulate cellular metabolic processes to promote their replication. Here, we review and discuss existing studies describing an interplay between carbohydrate metabolism and the replication cycle of herpesviruses, altogether highlighting potentially new molecular targets based on these interactions that could be used to block herpesvirus infections.

Novel Adjuvant S-540956 Targets Lymph Nodes and Reduces Genital Recurrences and Vaginal Shedding of HSV-2 DNA When Administered with HSV-2 Glycoprotein D as a Therapeutic Vaccine in Guinea Pigs.

Herpes simplex virus type 2 (HSV-2) is a leading cause of genital ulcer disease and a major risk factor for acquisition and transmission of HIV. Frequent recurrent genital lesions and concerns about transmitting infection to intimate partners affect the quality of life of infected individuals. Therapeutic vaccines are urgently needed to reduce the frequency of genital lesions and transmission. S-540956 is a novel vaccine adjuvant that contains CpG oligonucleotide ODN2006 annealed to its complementary sequence and conjugated to a lipid that targets the adjuvant to lymph nodes. Our primary goal was to compare S-540956 administered with HSV-2 glycoprotein D (gD2) with no treatment in a guinea pig model of recurrent genital herpes (studies 1 and 2). Our secondary goals were to compare S-540956 with oligonucleotide ODN2006 (study1) or glucopyranosyl lipid A in a stable oil-in-water nano-emulsion (GLA-SE) (study 2). gD2/S-540956 reduced the number of days with recurrent genital lesions by 56%, vaginal shedding of HSV-2 DNA by 49%, and both combined by 54% compared to PBS, and was more efficacious than the two other adjuvants. Our results indicate that S-540956 has great potential as an adjuvant for a therapeutic vaccine for genital herpes, and merits further evaluation with the addition of potent T cell immunogens.

Seroprevalence of Herpes Simplex Viruses Types 1 and 2 in a Population, Age 15-35 Years, of Mashhad City.

Background: Considering the high prevalence and clinical importance of herpes simplex virus (HSV) infection worldwide, we aimed to evaluate the seroprevalence of HSV-1 and HSV-2 in a population aged between 15 and 35 years in Mashhad, Iran. Methods: This cross-sectional study was conducted on 916 cases composed of 288 (31.4%) men and 628 (68.6%) women. Using ELISA method, the presence of IgM and IgG antibodies against HSV-1 and HSV-2 was assessed. Results: Among the population studied, 681 (74.3%) cases were positive for anti-HSV antibodies, while 235 (25.7%) cases were negative. Moreover, no IgMs were found and all positive subjects had IgG antibodies. Age (p < 0.001), occupation (p < 0.001), education (p = 0.006), smoking (p = 0.029), and BMI (p = 0.004) demonstrated a significant association with HSV-1 and HSV-2 infection. Conclusion: Our study indicates a high seroprevalence of HSV infection; however, there was no cases positive for IgM antibodies, suggesting the high prevalence of latent infection.

Association between human papillomavirus infection and common sexually transmitted infections, and the clinical significance of different Mycoplasma subtypes.

Introduction: Human papillomavirus (HPV) infection, especially persistent high-risk HPV, is associated with cervical cancer. Female reproductive tract microecological disorders and lower genital tract infections have been increasingly correlated with HPV infection and cervical lesions. Due to their common risk factors and transmission routes, coinfection with other sexually transmitted infections (STIs) has become a concern. Additionally, the clinical significance of Mycoplasma subtypes appear to vary. This study aimed to assess the correlations between common STIs and HPV infection, and to investigate the clinical significance of Mycoplasma subtypes. Methods: We recruited 1,175 patients undergoing cervical cancer screening at the Peking University First Hospital gynecological clinic from March 2021 to February 2022 for vaginitis and cervicitis tests. They all received HPV genotyping and detection of STIs, and 749 of them underwent colposcopy and cervical biopsy. Results: Aerobic vaginitis/desquamative inflammatory vaginitis and STIs (mainly single STIs) were found significantly more often in the HPV-positive group than in the HPV-negative group. Among patients with a single STI, rates of infection with herpes simplex virus type 2 or UP6 in the HPV-positive group were significantly higher than in the HPV-negative group (ORadj: 1.810, 95%CI: 1.211-2.705, P=0.004; ORadj: 11.032, 95%CI: 1.465-83.056, P=0.020, respectively). Discussion: Through detailed Mycoplasma typing, a correlation was found between different Mycoplasma subtypes and HPV infection. These findings suggest that greater attention should be paid to detecting vaginal microecological disorders in those who are HPV-positive. Further, lower genital tract infections, including both vaginal infections and cervical STIs, are significantly more common among women who are HPV-positive and who thus require more thorough testing. Detailed typing and targeted treatment of Mycoplasma should become more routine in clinical practice.