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The host enzyme heparanase (HPSE) facilitates the release of herpes simplex virus type 2 (HSV-2) from target cells by cleaving the viral attachment receptor heparan sulfate (HS) from infected cell surfaces. HPSE 2, an isoform of HPSE, binds to but does not possess the enzymatic activity needed to cleave cell surface HS. Our study demonstrates that HSV-2 infection significantly elevates HPSE 2 protein levels, impacting two distinct stages of viral replication. We show that higher HPSE 2 negatively affects HSV-2 replication which may be through the regulation of cell surface HS. By acting as a competitive inhibitor of HPSE, HPSE 2 may be interfering with HPSE's interactions with HS. We demonstrate that the enhanced expression of HPSE 2, either via viral infection or plasmid transfection, reduces HPSE's ability to cleave HS, thereby hindering viral egress. Conversely, low HPSE 2 levels achieved through siRNA transfection allow HPSE to cleave more HS, reducing viral entry. Altogether, we propose a hypothetical model in which the modulation of HPSE 2 impedes HSV-2 replication by regulating HS availability on the cell surface. This dual role of HPSE 2 in viral replication and potential tumor suppression underscores its significance in cellular processes and viral pathogenesis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Medicinal plants are the primary treatment for many infectious and non-infectious diseases. In this study, we evaluated the antiviral activity of Ferula assa-feotida against herpes simplex viruses 1 and 2, and compared it with the antiviral drug acyclovir. Materials and Methods: In our experimental study, Ferula assa-feotida was dissolved in DMSO, then diluted in DMEM medium. Acyclovir was used at a concentration of 100 µM in all procedures. The antiherpetic activity and Antiviral activity of Ferula were evaluated in Vero cells (African green monkey kidney cells) by using the plaque reduction assay. Results: Inhibitory concentrations of 50% (IC) of Ferula assa-feotida for HSV-1 and HSV-2 were determined at 0.00025% and 0.00015%, respectively. Ferula was introduced at various stages of viral infection and significantly inhibited HSV-1 and HSV-2 infectivity by > 95.5% and 89%, respectively, when virus was pre-treated before addition to the cells. No HSV-1 or HSV-2 activity was detected in cells treated prior to and following viral infection. Conclusion: These results indicate that Ferula assa-feotida demonstrates antiherpetic activity in the early phase of viral infection and could be used as potential antiviral agent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Depot-medroxyprogesterone acetate (DMPA) and Norethisterone Enanthate (NET-EN) are progestin-only injectable contraceptives widely used by women in sub-Sharan Africa, where incidence of HIV-1 and HSV-2 infection remains high. Studies indicate that DMPA usage can increase the risk of HSV-2 infection, but limited data indicate no increased risk with use of NET-EN. We therefore investigated the effects of NET-EN and DMPA on susceptibility to vaginal HSV-2 infection in ovariectomized (OVX) mice and effects on immune responses, particularly in the vaginal tract (VT). OVX mice, when treated with NET-EN and infected intravaginally, had delayed genital pathology, decreased viral shedding, and extended survival compared to DMPA- or untreated OVX mice. CD4+ T cells isolated from VT showed no significant change in frequency with either contraceptive. However, DMPA significantly decreased the total number of VT CD4+ and CD8+ T cells and the number of IFN-γ producing CD4 and CD8 T cells and increased the percentage of CD4 and CD8 T cells producing TNF-α compared to untreated mice. In contrast, NET-EN significantly enhanced percentages of CD8+ T cells compared to DMPA treated mice, and frequencies of IFN-γ+ CD4 and CD8 T cells in the VT compared to untreated mice. Comparative analysis of splenic lymphocytes indicated that DMPA treatment resulted in reduction of CD4+ T cell frequency, but enhanced TNF-α+ CD4 T cells compared to untreated mice. NET-EN enhanced the frequency of CD8 T cells, as well as IFN-γ+ and TNF-α+ CD4, and IFN-γ+ CD8 T cells in the spleen compared to untreated mice. Importantly, we found DMPA treatment that significantly reduced mucin production, whereas NET-EN enhanced expression of cell-associated mucin in VT. High levels of mucin in NET-EN mice were associated with lower levels of HSV-2 virus detected in the vaginal tract. This study provides the first evidence that NET-EN treatment can delay HSV-2 infection compared to DMPA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Depot-medroxyprogesterone acetate (DMPA) and Norethisterone Enanthate (NET-EN) are progestin-only injectable contraceptives widely used by women in sub-Sharan Africa, where incidence of HIV-1 and HSV-2 infection remains high. Studies indicate that DMPA usage can increase the risk of HSV-2 infection, but limited data indicate no increased risk with use of NET-EN. We therefore investigated the effects of NET-EN and DMPA on susceptibility to vaginal HSV-2 infection in ovariectomized (OVX) mice and effects on immune responses, particularly in the vaginal tract (VT). OVX mice, when treated with NET-EN and infected intravaginally, had delayed genital pathology, decreased viral shedding, and extended survival compared to DMPA- or untreated OVX mice. CD4+ T cells isolated from VT showed no significant change in frequency with either contraceptive. However, DMPA significantly decreased the total number of VT CD4+ and CD8+ T cells and the number of IFN-γ producing CD4 and CD8 T cells and increased the percentage of CD4 and CD8 T cells producing TNF-α compared to untreated mice. In contrast, NET-EN significantly enhanced percentages of CD8+ T cells compared to DMPA treated mice, and frequencies of IFN-γ+ CD4 and CD8 T cells in the VT compared to untreated mice. Comparative analysis of splenic lymphocytes indicated that DMPA treatment resulted in reduction of CD4+ T cell frequency, but enhanced TNF-α+ CD4 T cells compared to untreated mice. NET-EN enhanced the frequency of CD8 T cells, as well as IFN-γ+ and TNF-α+ CD4, and IFN-γ+ CD8 T cells in the spleen compared to untreated mice. Importantly, we found DMPA treatment that significantly reduced mucin production, whereas NET-EN enhanced expression of cell-associated mucin in VT. High levels of mucin in NET-EN mice were associated with lower levels of HSV-2 virus detected in the vaginal tract. This study provides the first evidence that NET-EN treatment can delay HSV-2 infection compared to DMPA.

Background: Herpes Simplex Virus Type 2 (HSV-2) is a prevalent sexually transmitted infection with varying clinical manifestations. Understanding the longitudinal outcomes is crucial for managing and mitigating its impact on individuals and public health. Material and Methods: In this cohort study, 100 participants from the general population were assessed over a defined follow-up period to determine the prevalence, symptomatic status, outbreak frequency, quality of life impact, treatment adherence, and transmission risks. Participants underwent serological testing and completed questionnaires regarding their symptoms, antiviral therapy, and quality of life. Results: Among the 100 participants, 32 tested positive for HSV-2, resulting in a prevalence rate of 32%. Of these, 22 (70%) were symptomatic, while 10 (30%) were asymptomatic. Symptomatic individuals experienced varying outbreak frequencies, with 31% suffering from 4-6 outbreaks annually. Quality of life was significantly impacted in symptomatic individuals across social (64%), psychological (68%), physical (42%), and financial (35%) domains. In the symptomatic group, 75% were on antiviral therapy, which effectively reduced outbreak frequency and severity. Viral shedding was detected in 31% of asymptomatic individuals, while 16% of asymptomatic individuals progressed to symptomatic during follow-up. Two partner transmission cases were recorded. Conclusion: The longitudinal outcomes of HSV-2 infection highlight the varied clinical course and significant psychosocial impact, underscoring the importance of consistent monitoring, individualized management, and effective educational programs to reduce transmission risk and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract 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.

The annual growth in the number of people living with HIV infection inevitably leads to an increase in the number of cases of any type of comorbidity. The article analyzes modern epidemiological, clinical, therapeutic aspects of anogenital herpes simplex virus infection (AHVI) in HIV-positive patients. Human immunodeficiency virus (HIV) and herpes simplex virus 2 (HSV-2) combine epidemiological and biological synergy. Concomitant anogenital herpes increases the risk of HIV infection by 2.74.7 times, and also contributes to its transmission through unprotected sexual intercourse. In HIV-infected patients with AHVI, the genital excretion of HSV-2 is increased. Among HIV-positive individuals, the seroprevalence of HSV-2 exceeds the population figures by 1.93.8 times. The incidence of AHVI in a cohort of Russians with a positive HIV status is 57.8 times higher than in the general population. The review demonstrates that both infections can have a negative mutual influence on the clinical course of each other. Particular emphasis is placed on the timely diagnosis of cases of coinfection. Based on the current regulatory documents, the authors developed and presented an algorithm for testing for HIV in patients with a newly diagnosed anogenital herpes.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-β. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Different adjuvants and immunization routes affect the protective efficacy of subunit vaccines. • gD plus AS02 induced highest neutralizing antibody titers. • gD plus AS02 tended to produce a more balanced immune reaction. • AS02 protected mice against a lethal dose of HSV-2 and completely eliminated the virus. • AS02 was beneficial for blocking HSV transmission. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Given malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity. Methods We established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single‐cell RNA sequencing. Furthermore, anti‐interleukin (IL)‐6R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL‐6 hypersecretion. Results OH2 was able to eliminate ascites and significantly prolong the survival of mice‐bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro‐inflammatory cytokines, mainly IL‐6, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5‐fluorouracil or nonresponders. Furthermore, the initial‐stage blocking of the IL‐6 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single‐cell RNA sequencing. Conclusions OH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL‐6, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy.

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. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus Type 2 (HSV-2) has been associated with depression, but the relationship has yet to be explored with respect to gender and sexual orientation in a nationally representative sample to help identify individuals at higher risk for depression. A dataset from National Health and Nutrition Examination Survey 2009–2014 was used in this study. Multivariable logistic regression models were constructed to test effect modification on both the multiplicative and additive scale using a sample of 57,684 subjects. Effect modification by sexual minority status was not significant on either the multiplicative scale (Ratio of ORs: 0.74, 95 % CI: 0.37–1.50, p = 0.395) or the additive scale (RERI: −0.22, 95%CI: −2.27–1.84, p = 0.833). Meanwhile, biological sex assigned at birth was a significant modifier only on the additive scale (RERI: 0.82, 95 % CI: 0.004–1.64, P = 0.049). Specifically, females (OR: 1.43, 95 % CI: 1.03–1.97, P = 0.032) had greater odds of having depressive symptoms compared with males (OR: 1.20, 95 % CI: 0.69–2.08, p = 0.509) after the HSV-2 infection. The analysis was based on a cross-sectional study; further investigation using longitudinal datasets might be beneficial. Sexual minority status did not modify the association between HSV-2 infection and having depressive symptoms. However, biological sex assigned at birth was a modifier only on the additive but not the multiplicative scale. Health workers should be alert for depression symptoms in females with HSV-2 infection. • Sexual minority status did not modify the association between HSV-2 infection and depression. • Biological sex was a modifier on the association between HSV-2 infection and depression only on the additive scale. • Females had greater odds of having depressive symptoms compared with males after the HSV-2 infection. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) infection, especially persistent highrisk 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. [ABSTRACT FROM AUTHOR]

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.

Introduction. Herpes simplex virus type 2 (HSV-2) is recognized as one of the most common causes of aseptic meningitis, that is also а well-known complication of genital herpes. We report a case of recurrent HSV-2 meningitis without genital lesions, but with simultaneous skin lesions that were a clue for diagnosis. Case presentation. A 21-year-old man had two episodes of aseptic meningitis in 2019 and 2021, respectively. During both episodes, the neurological manifestations were preceded by recurrent herpetic skin lesions on the right arm. HSV-2 deoxyribonucleic acid (DNA) was detected in the spinal fluid only in the first episode. However, due to the possibility that the lesions and simultaneous episodes of meningitis were caused by HSV-2, systemic acyclovir was initiated. Each time, the treatment was followed by rapid symptoms’ resolution. After the second episode, the patient was put on indefinite suppressive therapy with valacyclovir. Conclusions. Recurrent skin lesions can suggest the probability of HSV-2 etiology of concomitant meningitis and justify the initiation of acyclovir. In all confirmed meningitis cases with HSV-2, counseling on this genital infection and the possibility of sexual spread should be considered.

IntroductionHuman 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.MethodsWe 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.ResultsAerobic 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).DiscussionThrough 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.

Mushrooms produce various classes of secondary metabolites that could be used as antivirals in the future. The aim of this study was to determine the antiviral activity of methanolic extracts obtained from two edible mushrooms, Boletus bellinii (B. bellinii) and Boletus subtomentosus (B. subtomentosus), collected from the north forests of Tunisia, against Herpes Simplex Virus type 2 and Coxsackie Virus B type 3. In vitro micro-inhibition assays and cytotoxicity screening were performed on Vero cells. The tested Boletus methanolic extracts were found to be non-cytotoxic at high doses (50% cytotoxic concentration – CC50 > 1 mg/mL) and exhibited relevant viral inhibition with 50% inhibitory concentration, i.e., IC50 of 3.60 ± 0.66 µg/mL and 35.70 ± 7.42 µg/mL for B. bellinii, and 5.67 ± 1.02 µg/mL and 56.88 ± 9.56 µg/mL for B. subtomentosus, against HSV-2 and CVB-3, respectively. Interestingly, Boletus methanolic extracts showed high selectivity index (SI) values against both viruses, with the highest values against HSV-2 (SI > 800). Both viral strains were inhibited when treated with extracts during the early stages of virus replication. Inonotusin A was isolated and identified as the compound responsible for these activities. The latter is a novel antiviral agent that may have clinical utility or serve as a lead compound for further development. This study is the first attempt to investigate the antiviral activity of inonotusin A, isolated from the genus Boletus. The information from the present work should be a valuable reference for future studies on the antiviral activity of inonotusin A. [ABSTRACT FROM AUTHOR]

Background: Given malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity. Methods: We established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single‐cell RNA sequencing. Furthermore, anti‐interleukin (IL)‐6R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL‐6 hypersecretion. Results: OH2 was able to eliminate ascites and significantly prolong the survival of mice‐bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro‐inflammatory cytokines, mainly IL‐6, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5‐fluorouracil or nonresponders. Furthermore, the initial‐stage blocking of the IL‐6 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single‐cell RNA sequencing. Conclusions: OH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL‐6, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy. [ABSTRACT FROM AUTHOR]

BackgroundThe association between Herpes simplex virus type 2 (HSV-2) infection, a common infectious disease that increases the incidence of multisystem diseases, and asthma was less well studied. The aim of this study was to investigate the association between HSV-2 infection and the prevalence of asthma.Materials and methodsWe used data from National Health and Nutrition Examination Survey (NHANES) 1999–2016 for analysis. The study population included was limited to those aged 20–45 years and contained complete information on HSV-2 infection and asthma. We calculated the prevalence of HSV-2, asthma, and HSV-2 combined with asthma separately. The association between HSV-2 infection and asthma was analyzed using multiple logistic regression. We also performed stratified analyses to reduce bias and to find sensitive cohorts.ResultsThe prevalence of HSV-2 infection was decreasing with change in time period (P for trend < 0.01), but the prevalence of asthma was increasing (P for trend < 0.01). The prevalence of HSV-2 infection was higher in those with asthma than in non-asthma participants. A positive association was found between HSV-2 infection and asthma [odds ratio (OR) = 1.15, 95% CI: 1.04–1.27]. Subgroup analysis showed that this positive association was more pronounced in participants who were male, White, 30 years ≤ age ≤ 40 years, body mass index (BMI) ≤ 28 kg/m2, 1.39 ≤ ratio of family income to poverty (PIR) < 3.49 and smokers.ConclusionThere was a positive association between HSV-2 infection and asthma, and participants who were male, White race, 30 years ≤ age < 40 years, BMI ≥ 28 kg/m2, 1.39 ≤ PIR < 3.49, and smokers should receive more attention.

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.

Herpes simplex type 2 (HSV-2) infection causes a significant life-long disease. Long-term side effects of antiviral drugs can lead to the emergence of drug resistance. Thus, propolis, a natural product derived from beehives, has been proposed to prevent or treat HSV-2 infections. Unfortunately, therapeutic applications of propolis are still limited due its poor solubility. To overcome this, a nanoparticle-based drug delivery system was employed. An ethanolic extract of propolis (EEP) was encapsulated in nanoparticles composed of poly(lactic-co-glycolic acid) and chitosan using a modified oil-in-water single emulsion by using the solvent evaporation method. The produced nanoparticles (EEP-NPs) had a spherical shape with a size of ~450 nm and presented satisfactory physicochemical properties, including positively charged surface (38.05 ± 7.65 mV), high entrapment efficiency (79.89 ± 13.92%), and sustained release profile. Moreover, EEP-NPs were less cytotoxic on Vero cells and exhibited anti-HSV-2 activity. EEP-NPs had a direct effect on the inactivation of viral particles, and also disrupted the virion entry and release from the host cells. A significant decrease in the expression levels of the HSV-2 replication-related genes (ICP4, ICP27, and gB) was also observed. Our study suggests that EEP-NPs provide a strong anti-HSV-2 activity and serve as a promising platform for the treatment of HSV-2 infections. [ABSTRACT FROM AUTHOR]

An epidemiological model is proposed to study the transmission dynamics of the herpes virus type 2, a sexually transmitted infectious disease. This model considers two states, susceptible and infected, divides the population into sexes, assumes only heterosexual contacts and includes different transmission rates depending on whether the transmission is woman–man or man–woman. Reported and prevalence series data are retrieved from several sources. We consider the inherent data survey errors and the sensitivity of the diagnosis tests (data uncertainty). To calibrate the model to the available data and their uncertainty, a novel technique is proposed in two steps: (1) the application of the estimation of distribution algorithm (EDA) to find sets of model parameter values close to the data uncertainty and (2) the application of a selection algorithm to get a reduced number of model parameter values whose model outputs capture accurately the data uncertainty. Then, we check its robustness, and we provide a prediction of the evolution of the infected over the next 4 years. From the technical point of view, we conclude that the proposed technique to calibrate probabilistically the model is reliable and robust. Also, it is able to provide confidence intervals for the model parameter values and the predictions. From the medical point of view, the model returns that the transmission woman–man is higher than the man–woman, according to recent literature, and there is a mild increasing trend in the number of infected people over the next years. [ABSTRACT FROM AUTHOR]

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus type 2 (HSV-2) seroprevalence has been shown to be a potential sign of infection in pregnant women, and it could be applied to check HSV-2 transmission. This study evaluated the anti-HSV-2 IgG prevalence in pregnant women who were referred to health centers in Urmia, Northwest of Iran, during 2014-2015. Methods: Serum samples were collected from 86 pregnant women and tested for Anti-HSV-2-specific IgG using a commercial enzyme-linked immunosorbent assays kit. Results: Five (5.8%) pregnant women showed the presence of Anti-HSV-2-specific IgG antibodies. Previous abortion was reported in 16 (19.7%) and 2 subjects in the seronegative and seropositive groups, respectively. Conclusion: Data from the present study indicate a lower number of HSV-2 seropositives among the pregnant women in Urmia. This reduction would be a result of low number of studied subjects used in the present study; hence, assessing a large sample is recommended.

Mollaret meningitis is a rare form of recurrent, self-resolving, aseptic meningitis with a high rate of return. Although it has been associated with several conditions, herpes simplex virus type 2 (HSV-2) is most common. Diagnosis requires recurrent (>3) episodes of aseptic meningitis as defined by pleocytosis in cerebrospinal fluid (CSF) with negative bacterial cultures. Management is controversial but focuses primarily on supportive care with a potential role for antiviral therapy in both treatment and prevention of recurrence. This case describes a 35-year-old male with fourteen prior episodes of meningitis presenting with a recurrence of symptoms. CSF studies showed an aseptic meningitis due to HSV-2. He was treated with antiviral therapy and ultimately discharged on daily valacyclovir for recurrence prevention. Increased awareness of this condition amongst emergency physicians may help reduce resource utilization and unnecessary antibiotics, while also enhancing appropriate follow-up and prevention of recurrence., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Querin et al.)

Herpes simplex virus (HSV) is an alpha herpes virus, with two subtypes: HSV-1 and HSV-2. HSV is one of the most prevalent sexually transmitted infections. It is the cause of severe neonatal infections and a leading cause of infectious blindness in the Western world. As of 2016, 13.2% of the global population ages 15–49 were existing with HSV-2 infection and 66.6% with HSV-1. This high prevalence of disease and the fact that resistance to current therapies is on the rise makes it imperative to develop and discover new methods of HSV prevention and management. Among the arsenal of therapies/treatments for this virus has been the development of a prophylactic or therapeutic vaccine to prevent the complications of HSV reactivation. Our current understanding of the immune responses involved in latency and reactivation provides a unique challenge to the development of vaccines. There are no approved vaccines currently available for either prophylaxis or therapy. However, there are various promising candidates in the pre-clinical and clinical phases of study. Vaccines are being developed with two broad focuses: preventative and therapeutic, some with a dual use as both immunotherapeutic and prophylactic. Within this article, we will review the current guidelines for the treatment of herpes simplex infections, our understanding of the immunological pathways involved, and novel vaccine candidates in development. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV) is an alpha herpes virus, with two subtypes: HSV-1 and HSV-2. HSV is one of the most prevalent sexually transmitted infections. It is the cause of severe neonatal infections and a leading cause of infectious blindness in the Western world. As of 2016, 13.2% of the global population ages 15–49 were existing with HSV-2 infection and 66.6% with HSV-1. This high prevalence of disease and the fact that resistance to current therapies is on the rise makes it imperative to develop and discover new methods of HSV prevention and management. Among the arsenal of therapies/treatments for this virus has been the development of a prophylactic or therapeutic vaccine to prevent the complications of HSV reactivation. Our current understanding of the immune responses involved in latency and reactivation provides a unique challenge to the development of vaccines. There are no approved vaccines currently available for either prophylaxis or therapy. However, there are various promising candidates in the pre-clinical and clinical phases of study. Vaccines are being developed with two broad focuses: preventative and therapeutic, some with a dual use as both immunotherapeutic and prophylactic. Within this article, we will review the current guidelines for the treatment of herpes simplex infections, our understanding of the immunological pathways involved, and novel vaccine candidates in development.

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.

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).

Reproductive tract infections have long been hypothesized to be risk factors for development of uterine fibroids, but few studies have investigated the issue. In our 2016 cross-sectional analysis from the Study of Environment, Lifestyle and Fibroids (2010–2018), a large Detroit, Michigan, community-based cohort study of 23- to 35-year-old African-American women with ultrasound fibroid screening, we found no association between a very prevalent reproductive tract infection, herpes simplex virus type 2 (HSV-2), and fibroids. With prospective data from the cohort (ultrasounds performed every 20 months over 5 years), we examined HSV-2's associations with fibroid incidence (among 1,208 women who were fibroid-free at baseline) and growth (among women with fibroids at baseline or diagnosed during the study). Using Cox proportional hazards models, we computed adjusted hazard ratios and 95% confidence intervals for fibroid incidence comparing HSV-2–seropositive women with HSV-2–seronegative women. The influence of HSV-2 infection on growth was assessed on the basis of the difference in fibroid size between successive ultrasounds (1,323 growth measures) using a linear mixed model, estimating the percent difference in growth scaled to 18 months. HSV-2 seropositivity was not associated with fibroid incidence (adjusted hazard ratio = 0.88, 95% confidence interval: 0.69, 1.12) or growth (estimated growth difference = 3.1%, 95% confidence interval: −5.8, 13.0). Women can be reassured that HSV-2 infection is unlikely to increase their risk of fibroid-related health problems, given these longitudinal measures. [ABSTRACT FROM AUTHOR]

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml). [ABSTRACT FROM AUTHOR]

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. • VP5 protein of oncolytic virus OH2 promotes apoptosis in A549 cells in vivo and in vitro. • VP5 protein triggers apoptosis-related signaling pathways and GO terms in A549 cells. • VP5 protein induces apoptosis in A549 cells through the TP53I3 gene. [ABSTRACT FROM AUTHOR]

Abstract Recognition of unusual manifestations such as disseminated HSV or HSV‐related hemophagocytic lymphohistiocytosis among individuals with impaired cellular immunity and prompt treatment initiation are essential for a favorable outcome.

The aim of the work was to study the activity of echinochrome A, a naphthoquinoid pigment from sea urchins, and its antioxidant composition against herpes simplex virus type 2 (HSV-2) in vitro and in vivo.Materials and methods. Strain HSV-2 (G ATCC VR-734) was grown in Vero cells. The cytotoxic and anti-HSV-2 activity of the compounds was assessed in vitro by the cell viability and by cytopathic effect inhibition of virus using MTT test. The efficacy of compounds in mice model of vaginitis caused by HSV-2 was determined by the average lifetime, body weight and viral load changes.Results and discussion. The antioxidant composition (echinochrome A, ascorbic acid and α-tocopherol (5:5:1)), showed a higher antiviral efficacy than echinochrome A alone. Oral administration of the antioxidant composition protected 90% of the infected mice against death and reduced vaginal viral loads. The antiviral activity of echinochrome A and the antioxidant composition is probably due to the virus-inhibiting activity of the compounds and their antioxidant properties.Conclusion. The results obtained allow considering the tested compounds as promising agents with antiviral properties.

Herpes simplex virus type 2 (HSV2), a pathogen that causes genital herpes lesions, interferes with the host immune system via various known and unknown mechanisms. This virus has been used to study viral antigenic composition. Convalescent serum from HSV2-infected patients was used to identify viral antigens via 2-D protein electrophoresis and immunoblotting. The serum predominantly recognized several capsid scaffold proteins encoded by gene UL26.5, mainly ICP35. This protein has been primarily reported to function temporarily in viral assembly but is not expressed in mature virus particles. Further immunological studies suggested that this protein elicits specific antibody and cytotoxic T lymphocyte (CTL) responses in mice, but these responses do not result in a clinical protective effect in response to HSV2 challenge. The data suggested that immunodominance of ICP35 might be used to design an integrated antigen with other viral glycoproteins.

Herpes simplex virus type 2 (HSV2), a pathogen that causes genital herpes lesions, interferes with the host immune system via various known and unknown mechanisms. This virus has been used to study viral antigenic composition. Convalescent serum from HSV2-infected patients was used to identify viral antigens via 2-D protein electrophoresis and immunoblotting. The serum predominantly recognized several capsid scaffold proteins encoded by gene UL26.5, mainly ICP35. This protein has been primarily reported to function temporarily in viral assembly but is not expressed in mature virus particles. Further immunological studies suggested that this protein elicits specific antibody and cytotoxic T lymphocyte (CTL) responses in mice, but these responses do not result in a clinical protective effect in response to HSV2 challenge. The data suggested that immunodominance of ICP35 might be used to design an integrated antigen with other viral glycoproteins. [ABSTRACT FROM AUTHOR]

Epithelial cells of the female reproductive tract (FRT) participate in the initial innate immunity against viral infections. Poly(dA:dT) is a synthetic analog of B form double-stranded (ds) DNA which can activate the interferon (IFN) signaling pathway-mediated antiviral immunity through DNA-dependent RNA Polymerase III. Here we investigated whether poly(dA:dT) could inhibit herpes simplex virus type 2 (HSV-2) infection of human cervical epithelial cells (End1/E6E7). We demonstrated that poly(dA:dT) treatment of End1/E6E7 cells could significantly inhibit HSV-2 infection. Mechanistically, poly(dA:dT) treatment of the cells induced the expression of the intracellular IFNs and the multiple antiviral IFN-stimulated genes (ISGs), including IFN-stimulated gene 15 (ISG15), IFN-stimulated gene 56 (ISG56), 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), myxovirus resistance protein A (MxA), myxovirus resistance protein B (MxB), virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible (Viperin), and guanylate binding protein 5 (GBP5). Further investigation showed that the activation of RIG-I was largely responsible for poly(dA:dT)-mediated HSV-2 inhibition and IFN/ISGs induction in the cervical epithelial cells, as RIG-I knockout abolished the poly(dA:dT) actions. These observations demonstrate the importance for design and development of AT-rich dsDNA-based intervention strategies to control HSV-2 mucosal transmission in FRT.

Background: As one of the most prevalent cancers in men, prostate cancer is a condition with multiple causes. Viral infections have been identified as one of the major sources of elevated incidence of prostate cancer. Objectives: The purpose of this research was to assess the association of the risk of prostate cancer and its aggressiveness with seropositivity of herpes simplex virus 2 (HSV-2) and/or human herpesvirus 8 (HHV-8). Methods: Totally, 103 men with prostate cancer as cases and 81 healthy individuals as controls were included in this case-control analysis and provided a serum sample. The specific IgG antibodies against HSV-2 and HHV-8 were screened by enzyme-linked immunosorbent assay (ELISA). To determine the association between HSV-2, HHV-8, prostate-specific antigen (PSA) level, and demographic variables with incidence of prostate cancer, univariate and multivariate logistic regression models were applied. Results: The results of the univariate logistic regression model showed a statistically significant association between HSV-2 and HHV-8 seropositivity, PSA level, age, and smoking with prostate cancer incidence (P ≤ after adjusting for the potential confounding variables showed a significant statistical association between the mean of PSA level [adjusted odds ratio (OR): 3.44; 95% CI: 2.15 - 5.51; P < 0.001) and incidence of prostate cancer. Moreover, the results of univariate and multivariate logistic regression model showed a significant statistical association between age [adjusted OR: 0.88; 95% confidence interval (CI): 0.81 - 0.95; P = 0.001] and HSV-2 and also significant statistical association was found between PSA (adjusted OR: 1.02; 95% CI: 1.005 - 1.03; P = 0.006) and HHV-8. Conclusions: Although the seroprevalence of HSV-2 and HHV-8 was higher in patients with prostate cancer than in the control group, it cannot be concluded that there is a significant association between the seropositivity of these viruses and prostate cancer incidence. However, the findings showed a significant statistical association between age and seropositivity of HSV-2 and also a significant statistical association between PSA levels and seropositivity of HHV-8. [ABSTRACT FROM AUTHOR]

Background: As one of the most prevalent cancers in men, prostate cancer is a condition with multiple causes. Viral infections have been identified as one of the major sources of elevated incidence of prostate cancer. Objectives: The purpose of this research was to assess the association of the risk of prostate cancer and its aggressiveness with seropositivity of herpes simplex virus 2 (HSV-2) and/or human herpesvirus 8 (HHV-8). Methods: Totally, 103 men with prostate cancer as cases and 81 healthy individuals as controls were included in this case-control analysis and provided a serum sample. The specific IgG antibodies against HSV-2 and HHV-8 were screened by enzyme-linked immunosorbent assay (ELISA). To determine the association between HSV-2, HHV-8, prostate-specific antigen (PSA) level, and demographic variables with incidence of prostate cancer, univariate and multivariate logistic regression models were applied. Results: The results of the univariate logistic regression model showed a statistically significant association between HSV-2 and HHV-8 seropositivity, PSA level, age, and smoking with prostate cancer incidence (P ≤ 0.20). The multivariate logistic regression model results after adjusting for the potential confounding variables showed a significant statistical association between the mean of PSA level [adjusted odds ratio (OR): 3.44; 95% CI: 2.15 - 5.51; P < 0.001) and incidence of prostate cancer. Moreover, the results of univariate and multivariate logistic regression model showed a significant statistical association between age [adjusted OR: 0.88; 95% confidence interval (CI): 0.81 - 0.95; P = 0.001] and HSV-2 and also significant statistical association was found between PSA (adjusted OR: 1.02; 95% CI: 1.005 - 1.03; P = 0.006) and HHV-8. Conclusions: Although the seroprevalence of HSV-2 and HHV-8 was higher in patients with prostate cancer than in the control group, it cannot be concluded that there is a significant association between the seropositivity of these viruses and prostate cancer incidence. However, the findings showed a significant statistical association between age and seropositivity of HSV-2 and also a significant statistical association between PSA levels and seropositivity of HHV-8. [ABSTRACT FROM AUTHOR]