Search Results (68)

Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article

Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle. Full article

Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic Republic of the Congo. Methods: A cross-sectional study was conducted among 432 FSWs (mean age, 28.1 years) recruited via respondent-driven sampling. Genital self-sampling using the V-Veil UP2™ device was performed, followed by HPV genotyping and quantification by multiplex PCR, and HSV-2 DNA detection by PCR. Results: Among 415 participants, HR-HPV prevalence was 36.9%, with HPV-52 (14.9%), HPV-58 (10.1%), and HPV-16 (6.5%) as leading genotypes. Overall, 89% of HR-HPV-positive women harbored genotypes covered by Gardasil-9^®. Co-infection with HIV and HSV-2 significantly increased HPV prevalence, genotype diversity, and viral load. Notably, HSV-2 positivity was the sole independent predictor of elevated replication of HR-HPV (p < 0.001), vaccine HR-HPV (p < 0.001), and non-vaccine HR-HPV (p < 0.021). Conclusions: FSWs exhibit a high burden of HR-HPV, shaped by co-infections with HIV and HSV-2. HSV-2 independently drives HR-HPV replication, highlighting its role in HPV persistence and cervical cancer risk. Integrated HSV-2 detection and Gardasil-9^® vaccination should be prioritized in cervical cancer elimination strategies targeting high-risk populations in sub-Saharan Africa. Full article

The general female population is not considered a high-risk group for screening for sexually transmitted infections (STIs). This retrospective study describes the prevalence of Human Immunodeficiency Virus (HIV), Treponema pallidum (T. pallidum), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Trichomonas vaginalis (T. vaginalis), Mycoplasma spp., Ureaplasma spp., genital Herpes simplex virus (HSV), Monkeypox (mpox), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infections in asymptomatic and symptomatic cisgender women attending our walk-in STI clinic for the first time. Furthermore, it analyzes the number of individuals who returned for follow-up and were diagnosed with new STIs. Over 20 months, 189 women with a median age of 28.4 years were screened [129 (68.3%) asymptomatic and 60 (31.8%) symptomatic]. In order of prevalence, the most common STIs were: Ureaplasma spp. infections (50.3%), C. trachomatis (10.6%), N. gonorrhoeae (5.8%), Mycoplasma hominis infections (5.8%), T. pallidum (2.65%), HSV2 infections (2.65%), and mpox (0.53%). No diagnosis of HIV, trichomoniasis, HBV, or HCV was registered. After the initial evaluation, 128 (67.7%) women returned for follow-up, but only 43 (22.8%) repeated screening; among them, 11 (25.6%) were diagnosed with new STIs. Given the high prevalence of STIs in cisgender women, awareness measures to improve screening and prevention strategies in this neglected population are required. Full article

Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate. Full article

Infections are an important cause of morbidity and mortality in renal transplant recipients. Among the viral pathogens encountered in this population, herpes simplex virus (HSV), a member of the Alphaherpesvirinae subfamily, has an important place. HSV type 2 infections in this immunosuppressed population are primarily due to viral reactivation. While HSV-2 frequently presents as genital herpes or remains asymptomatic, in rare cases, it can lead to severe neurological manifestations, such as encephalitis, particularly in the early post-transplant period with a reported mortality rate of up to 40%. We present the case of a 49-year-old male who, three years after kidney transplantation, developed acute neurological symptoms, including aphasia and disorientation. Polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) identified HSV-2 as the causative pathogen, enabling a swift and accurate diagnosis. The patient was promptly treated with intravenous acyclovir, adjusted for renal function, resulting in complete neurological recovery and subsequent negative follow-up CSF PCR results. This case emphasizes the vital role of PCR diagnostics as the gold standard for confirming viral encephalitis, particularly in immunosuppressed patients, where atypical presentations can complicate diagnosis. It also highlights the importance of considering HSV-2 encephalitis in the differential diagnosis even beyond the immediate post-transplant period. Early recognition and management, facilitated by the multidisciplinary approach, are critical for improving outcomes in this vulnerable patient population. Full article

Sub-Saharan Africa (SSA) bears a disproportionate and overlapping burden of soil-transmitted helminths (STHs) and sexually transmitted viral infections. An estimated 232 million pre-school and school-aged children in SSA are vulnerable to STH infections. Together with this, SSA has a high prevalence of herpes simplex virus type II (HSV-2), the primary cause of genital herpes. Studies have examined the immunological interactions between STHs and human immunodeficiency virus and human papillomavirus during co-infections. However, epidemiological and immunological studies on STH-HSV-2 co-infections are lacking, therefore their impact on sexual and reproductive health is not fully understood. STH-driven Th2 immune responses are known to downregulate Th1/Th17 immune responses. Therefore, during STH-HSV-2 co-infections, STH-driven immune responses may alter host immunity to HSV-2 and HSV-2 pathology. Herein, we provide an overview of the burden of STH and HSV-2 infections in SSA, and host immune responses to STH and HSV-2 infections. Further, we emphasize the relevance and urgent need for (i) focused research into the interactions between these important pathogens, and (ii) integrated approaches to improve the clinical detection and management of STH-HSV-2 co-infections in SSA. Full article

Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a “viral relay” to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4⁺ and CD8⁺ T cells. Full article

Genital herpes simplex virus (HSV) is associated with a reduction in quality of life and adverse outcomes. The aim of this study is to assess the interest and expectations for a therapeutic HSV vaccine among individuals diagnosed with genital herpes in Italy. A retrospective survey was conducted at the Infectious Diseases Unit of the IRCCS San Raffaele Scientific Institute, Milan, Italy. The study collected data on demographics, clinical history and interest in HSV vaccination. The results showed that 87.5% of participants were interested in a therapeutic vaccine, with interest higher among younger people and those with frequent genital herpes recurrences. Participants most expected the vaccine to reduce the pain associated with outbreaks, followed by a reduction in the frequency and duration of recurrences. These findings underscore the strong demand for a therapeutic HSV vaccine, especially among those who experience recurrent outbreaks, and highlight the importance of considering patient expectations when developing preventive and therapeutic strategies for genital herpes. Full article

Viral outbreaks are common in the sport community. Data regarding the prevalence of plantar warts, genital warts, herpes simplex type 1 (herpes labialis), herpes zoster, and genital herpes in competitive swimmers are lacking in the literature. The purpose of this study was to determine the prevalence of those viral infections among young competitive swimmers participating in Greek swimming clubs. Swimmers’ parents and adult swimmers were asked to complete an anonymous questionnaire. In total, 1047 swimmers enrolled in this study. The measured parameters included gender, age, times of infections, and seasons when athletes may be more susceptible to infections. Practicing information such as type of swimming facility, number of training years, average hours of daily training, behaviors in swimming practice, and sunlight exposure was also recorded. All infections showed a significant difference in relation to “age” and “years of training”. The gender significance was observed in herpes labialis (p = 0.016) and plantar warts (p = 0.05). The prevalence of all infections in swimmers who use outdoor facilities was higher. Certain behaviors such as walking barefoot on a pool deck and sharing swimming equipment correlate with herpes simplex and plantar warts. Virus infections can affect swimmers of all ages. In our study, plantar warts and herpes labialis are more common in swimmers. Herpes zoster and sexually transmitted viruses are rarer and affect adult swimmers. The impact of cutaneous infections on swimmers can affect performance and well-being. Effective prevention and management are essential to avoid complications. Proper hygiene, medical guidance, and treatment reduce swimmers’ exposure to skin viruses. Full article

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

Alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV), infect a diverse array of hosts, spanning both humans and animals. Alphaherpesviruses have developed a well-adapted relationship with their hosts through long-term evolution. Some alphaherpesviruses exhibit a typical neurotropic characteristic, which has garnered widespread attention and in-depth research. Virus latency involves the retention of viral genomes without producing infectious viruses. However, under stress, this can be reversed, resulting in lytic infection. Such reactivation events can lead to recurrent infections, manifesting as diseases like herpes labialis, genital herpes, and herpes zoster. Reactivation is a complex process influenced by both viral and host factors, and identifying how latency and reactivation work is vital to developing new antiviral therapies. Recent research highlights a complex interaction among the virus, neurons, and the immune system in regulating alphaherpesvirus latency and reactivation. Neurotropic alphaherpesviruses can breach host barriers to infect neurons, proliferate extensively within their cell bodies, and establish latent infections or spread further. Whether infecting neurons or spreading further, the virus undergoes transmission along axons or dendrites, making this process an indispensable part of the viral life cycle and a critical factor influencing the virus’s invasion of the nervous system. Research on the transmission process of neurotropic alphaherpesviruses within neurons can not only deepen our understanding of the virus but can also facilitate the targeted development of corresponding vaccines. This review concentrates on the relationship between the transmission, latency, and activation of alphaherpesviruses within neurons, summarizes recent advancements in the field, and discusses how these findings can inform the design of live virus vaccines for alphaherpesviruses. Full article

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that causes a persistent infection in sensory ganglia. The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection. Full article

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20–25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies. Full article

From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (T_RM) CD8+ T cells that accumulate and persist in the genital skin at the local site of recrudescence are the “first responders” to viral reactivation, performing immunosurveillance and containment and aborting the ability of the virus to induce clinical lesions. This review describes the unique spatiotemporal characteristics, transcriptional signatures, and noncatalytic effector functions of T_RM CD8+ T cells in the tissue context of human HSV-2 infection. We highlight recent insights into the intricate overlaps between intrinsic resistance, innate defense, and adaptive immunity in the tissue microenvironment and discuss how rapid virus–host dynamics at the skin and mucosal level influence clinical outcomes of genital herpes diseases. Full article