Genital HSV-2 Research Articles

Murine Skin-resident γδT Cells Impair the Immune Response to HSV in Skin.

HSV is an important cause of brain infection. Virus entry is often through breeches in the skin. γδT cells play an immunoprotective role in mice after corneal, genital or footpad (subcutaneous) HSV infection. Here we report that the presence of γδT cells in murine skin is associated with increased severity of herpetic disease, reduced protective cytokine responses and increased viral spread from the skin to the sensory ganglia in the zosteriform model. γδT cell-deficient (TCR δ -/-) mice displayed significantly decreased herpetic lesion severity after flank HSV infection compared to WT C57BL/6 controls at both primary and secondary skin infection sites. Viral titer at the primary skin site was similar to WT mice in γδT cell-deficient mice, but was significantly decreased in the ganglia and secondary skin site. γδT cell-deficient mice showed increased Th1 responses by both T cells and non-T cells at the primary site, and decreased T-cell Th17 responses and immune infiltration at the secondary site. Cytokine responses of epidermal and dermal γδT cells to HSV also differed in WT mice (Th1 in epidermis, and Th17 in the dermis), suggesting a functional dichotomy between these two subsets. Our data suggest that in contrast to other mouse models of HSV infection, skinresident γδT cells promote the pathogenesis of HSV in skin.

Characteristics of genital herpes in Bilbao (Northern Spain): 12-year retrospective study

BackgroundHerpes simplex virus type 2 (HSV-2) is the most common cause of genital herpes (GH), but genital infection by herpes simplex virus type 1 (HSV-1) is increasing. The aim of this study was to analyze and compare epidemiological characteristics of patients with GH. MethodsRetrospective study conducted from January 2004 to December 2015 in patients with GH attended at two Sexually Transmitted Diseases (STDs) medical consultation of Bilbao-Basurto Integrated Health Organisation in Northern Spain. Patient's medical history was reviewed and data of interest was analyzed. ResultsOne thousand three patients (524 male and 479 female) were reviewed. HSV-2 was detected in 74%. The proportion of HSV-1 increased during the study period, significantly in men (28% in 2004–2007 vs. 50% in 2012–2015). More female than male had HSV-1 infection (56% vs. 44%). The proportion of primary infection was higher among HSV-1 compared to HSV-2 (79% vs. 21%). Among the patients with HSV-1, primary infection was higher among men (86%) and in younger than 30 years. Recurrent GH was higher among HSV-2 infections (63%). In a multivariate model older age, geographic origin outside Spain, recurrent infection, prior contact with a partner's genital herpetic lesions, previous N. gonorrhoeae infection and prostitution were significantly associated with HSV-2 infection. ConclusionsHSV-2 was the most common causative agent of GH, but the proportion of HSV-1 increased. Overall, antecedent of STD and sexual risk behaviors were more frequent in patients with genital HSV-2 infection.

The global and regional burden of genital ulcer disease due to herpes simplex virus: a natural history modelling study

IntroductionHerpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due...

Herpes in Pregnancy

AbstractHerpes simplex virus infection (predominantly HSV2) in pregnancy can be a cause of maternal morbidity. The more serious cause of concern is perinatal transmission of infection resulting in neonatal morbidity and mortality. Genital HSV infection can be primary, non-primary first episode or recurrent infection. Clinical and laboratory diagnosis in pregnant women is similar to non-pregnant women. Direct viral testing (PCR) from lesion's and type specific serology are required to classify type of infection. Vertical transmission occurs during labor and delivery. The risk is higher in primary and non-primary first episode near the time of delivery. Antiviral treatment with Acyclovir or Valacyclovir is recommended for acute episode to reduce lesion duration and viral shedding. Acyclovir as suppressive therapy from 36 weeks onwards reduces clinical recurrences and need for caesarean delivery. Caesarean section reduces but does not eliminate the risk of vertical transmission and is recommended for a woman has an acute infection episode at the time of labor or within 6 weeks before delivery. Clinical management of preterm premature rupture of membranes in a woman with HSV infection should be individualized. All neonates born to these mothers should be carefully handled and monitored for development of neonatal herpes.

IL-36γ Is a Key Regulator of Neutrophil Infiltration in the Vaginal Microenvironment and Limits Neuroinvasion in Genital HSV-2 Infection.

HSV-2 is a neurotropic virus that causes a persistent, lifelong infection that increases risk for other sexually transmitted infections. The vaginal epithelium is the first line of defense against HSV-2 and coordinates the immune response through the secretion of immune mediators, including the proinflammatory cytokine IL-36γ. Previously, we showed that IL-36γ treatment promoted transient polymorphonuclear cell infiltration to the vaginal cavity and protected against lethal HSV-2 challenge. In this report, we reveal that IL-36γ specifically induces transient neutrophil infiltration but does not impact monocyte and macrophage recruitment. Using IL-36γ-/- mice in a lethal HSV-2 challenge model, we show that neutrophil counts are significantly reduced at 1 and 2 d postinfection and that KC-mediated mature neutrophil recruitment is impaired in IL-36γ-/- mice. Additionally, IL-36γ-/- mice develop genital disease more rapidly, have significantly reduced survival time, and exhibit an increased incidence of hind limb paralysis that is linked to productive HSV-2 infection in the brain stem. IL-36γ-/- mice also exhibit a significant delay in clearance of the virus from the vaginal epithelium and a more rapid spread of HSV-2 to the spinal cord, bladder, and colon. We further show that the decreased survival time and increased virus spread observed in IL-36γ-/- mice are not neutrophil-dependent, suggesting that IL-36γ may function to limit HSV-2 spread in the nervous system. Ultimately, we demonstrate that IL-36γ is a key regulator of neutrophil recruitment in the vaginal microenvironment and may function to limit HSV-2 neuroinvasion.

A vaccine containing highly purified virus particles in adjuvant provides high level protection against genital infection and disease in guinea pigs challenged intravaginally with homologous and heterologous strains of herpes simplex virus type 2

Infection with Herpes Simplex Viruses (HSVs) represents a significant health burden worldwide with HSV-1 and HSV-2 causing genital disease and HSV-2 contributing to human immunodeficiency virus acquisition. Despite great need, there is currently no licensed vaccine against HSV. In this report, we evaluated the protective efficacy of a vaccine containing highly purified, inactivated HSV-2 particles (with and without additional recombinant glycoprotein D) formulated with a monophosphoryl lipid A/Alhydrogel adjuvant in a guinea pig HSV genital model. The key results from 3 independent studies were: (1) vaccination consistently provided significant 3–3.5 Log10 reductions in vaginal HSV-2 titers on day 2 postchallenge; (2) following homologous or heterologous challenge with two U.S. isolates, all vaccine groups showed complete protection against lesion formation, significant 3 Log10 reductions in day 2 virus shedding, enhanced virus clearance, significant reductions in HSV-2 DNA within ganglia, and no detectable shedding (<2 PFU) or latent viral DNA in some immunized animals; (3) following challenge with a third heterologous strain, vaccination provided complete protection against primary and recurrent lesions, significant reductions in primary virus shedding, a 50% reduction in recurrent shedding days, and undetectable latent virus in the ganglia and spinal cords of most animals; and (4) adding glycoprotein D provided no enhanced protection relative to that elicited by the inactivated HSV-2 particles alone. Together, these data provide strong support for further development of this exceedingly protective and highly feasible vaccine candidate for human trials.

Abstract CT040: A Phase I trial of talimogene laherparepvec combined with neoadjuvant chemotherapy for non-metastatic triple negative breast cancer

Abstract BACKGROUND: Talimogene laherparepvec (TVEC) is a modified oncolytic herpes simplex 1 (HSV1) virus currently FDA approved for the treatment of melanoma. TVEC preferentially lyses tumor cells over normal tissue to release tumor associated antigens, produces GM-CSF to activate dendritic cells, and stimulates T cells to infiltrate the tumor (TILs). TILs in breast cancer are associated with better response to neoadjuvant chemotherapy (NAC), so we hypothesized that intratumoral TVEC may enhance response to NAC. We report safety and outcomes of a Phase I trial combining NAC with TVEC in stage 2-3 TNBC. METHODS: Stage 2-3 TNBC patients were enrolled into a 3+3 Phase I trial with 2 TVEC dose levels [DL1=106 PFU x 5 doses, DL2=106 PFU 1st dose then 108 PFU x 4 doses] q2week + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone. Patients then had surgery and were assessed for pathologic complete response (pCR). Primary endpoint is safety by CTCAE 4.03 and maximum tolerated dose (MTD), secondary is pCR rate and immune correlates. Dose limiting toxicity (DLT) rule was grade 3-5 adverse event due to TVEC during 1st 6 weeks. RESULTS: Nine patients (DL1 [n=3], DL2 [n=6]) were enrolled. Six pts were stage II, three were stage III (6 clinically N+). No DLTs were encountered and MTD dose was DL2. Most common toxicities due to TVEC were fevers (n=8), chills (n=3), hematomas (n=3), injection site pain (n=3). One genital wild type HSV1 reactivation event occurred. Common NAC related toxicities included anemia, nausea, fatigue, neuropathy, infusion reactions, lymphopenia as expected. Thromboembolic events (n=2) and severe bradycardia (n=1) occurred during or after AC chemo. Five pts (55%) had pCR, 2 had microscopic residual disease (22%), 2 had gross residual disease (22%). Preliminary immune correlates show heavy immune infiltration in analyzed tumors, full results will be presented. CONCLUSION: Addition of TVEC to NAC was feasible at full FDA approved dose with manageable toxicity. The combination is highly active in TNBC with an increase in pCR rate (55%) over expected rate of 30% with NAC alone. Preliminary evidence of robust immune activation was observed. This combination will continue to be evaluated in an ongoing phase II trial. Citation Format: Hatem Soliman, Deanna Hogue, Hyo Han, Blaise Mooney, Ricardo Costa, Marie C. Lee, Bethany Niell, Nazanin Khakapour, Robert J. Weinfurtner, Susan Hoover, Marilin Rosa, Hung Khong, Brian Czerniecki. A Phase I trial of talimogene laherparepvec combined with neoadjuvant chemotherapy for non-metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT040.

IL-36γ regulates neutrophil infiltration and limits neuroinvasion in genital HSV-2 pathogenesis

Abstract Herpes simplex virus 2 is a neurotropic virus that causes a persistent, life-long infection that increases risk for other sexually transmitted infections. The vaginal epithelium is the first line of defense against HSV-2 and secretes immune mediators, including the pro-inflammatory cytokine IL-36γ, to coordinate the immune response. Previously, we showed that IL-36γ treatment promoted polymorphonuclear cell infiltration to the vaginal cavity and protected against lethal HSV-2 challenge. Herein, we extended these findings using flow cytometry to profile the cellular infiltrate. IL-36γ significantly (p &amp;lt; 0.0001) induced transient neutrophil infiltration, but did not impact monocyte or macrophage recruitment. Using IL-36γ−/− mice in a lethal HSV-2 challenge model, we show that neutrophils were significantly (p &amp;lt; 0.0001) depleted at 1- and 2-days post infection, and that mature neutrophil recruitment was impaired. In addition, IL-36γ−/− mice develop genital disease more rapidly (p &amp;lt; 0.0001), have significantly (p &amp;lt; 0.0001) reduced survival time, and display an increased incidence (p &amp;lt; 0.0001) of neurologic disease compared to wild type mice. IL-36γ−/− mice exhibited a significant (p &amp;lt; 0.05) delay in clearance of the virus from the vaginal epithelium, and analysis of virus spread to the spinal cord, bladder, and colon demonstrated that HSV-2 spread significantly (p &amp;lt; 0.05) more quickly in IL-36γ−/− mice. Further, we detected productive HSV-2 infection in the brainstem of IL-36γ−/− mice significantly (p &amp;lt; 0.0001) more frequently than in wild type mice. Ultimately, we demonstrate that IL-36γ is a key regulator of neutrophil recruitment in the vaginal microenvironment and may function to limit HSV-2 neuroinvasion.

Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome.

Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

Genital Symptoms and Genital Hsv-2 and Hiv-1 Shedding In Co-Infected Women — Chiang Rai, Thailand

1Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA 2Division of Applied Sciences, Epidemic Intelligence Service, Scientific Education and Professional Development Program Office, Centers for Disease Control and Prevention, Atlanta, GA, USA 3Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA 4Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA 5Thailand Ministry of Public Health-US CDC Collaboration, Nonthaburi, Thailand Research Open Access

The Effect of Hormonal Contraception and Menstrual Cycle Timing on Genital Herpes Simplex Virus-2 Shedding and Lesions.

The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use. In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03-1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66). In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

Synthesis of pseudoboehmite-graphene oxide for drug delivery system

Abstract Pseudoboehmite is a hydrated aluminium compound produced by sol-gel process and used in drug delivery systems. The graphene oxide is a material that allows for many possibilities application as modify agent in a ceramic structure. The global prevalence and incidence of herpes simplex virus infections (HSV-1 and HSV-2) have risen worldwide. A big problem is that most persons with genital HSV infection have not received a diagnosis. Other concerning situation is that the herpes infected patients are more susceptible to HIV infections. It is also observed that in women the HSV infection are more common than in men. Acyclovir is an efficient drug for the treatment of herpes viruses. However, the oral bioavailability of acyclovir is limited due to varying and incomplete absorption. In this work, pseudoboehmite was produced with incorporation of graphene oxide in the gel. The pseudoboehmite-graphene oxide was used in in vitro drug delivery system for acyclovir.

The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes

BackgroundAlthough development of an HSV vaccine is a priority there is currently no vaccine available. The recent failure of subunit vaccines suggest that presentation of more antigens via a live attenuated vaccine may be required for protection. We therefore evaluated VC2, a live attenuated HSV vaccine, engineered to be unable to enter into neuronal axons. MethodsVC2 pathogenesis was first evaluated in guinea pigs following intravaginal inoculation. VC2 was then evaluated as a prophylactic and therapeutic vaccine and compared protection to a gD2 vaccine adjuvanted with MPL/Alum in the guinea pig model of genital HSV-2. The guinea pig model allows evaluation of acute and recurrent disease, as well as vaginal shedding acutely and during episodes of recurrent activation. ResultsVC2 was significantly attenuated in guinea pigs compared to the wild type strain, 17syn+. It replicated poorly at the inoculation site, did not produce any genital disease and rarely infected the neural tissue. After prophylactic vaccination, the VC2 vaccine decreased the clinical severity of acute and recurrent HSV-2 disease and shedding and decreased the quantity of virus in the DRGs. When compared to gD2+MPL/Alum, VC2 was somewhat more effective especially as it relates to neural tissue infection. VC2 was not effective as a therapeutic vaccine. ConclusionThe live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over other live attenuated vaccines.

Female sex hormones regulate the IL-36 family members in the female reproductive tract and impact HSV-2 pathogenesis

Abstract Recently, the contraceptive Depo-Provera (DMPA) has been linked to an increased risk of sexually transmitted infection acquisition (e.g. HSV-2 and HIV). However, a fundamental gap exists in the understanding of specific mechanisms whereby DMPA use increases risk for HSV-2 infection. IL-36γ is a novel regulator of mucosal inflammation in the female reproductive tract (FRT) and we have shown that IL-36γ is induced in response to HSV-2. One study reported that IL-36γ was the only cytokine upregulated in cervicovaginal secretions from HSV-2 seropositive DMPA users, suggesting that IL-36γ may be a link between DMPA use and HSV-2 infection. We hypothesize that DMPA suppresses IL-36γ expression in the vaginal environment, thereby increasing susceptibility to genital HSV-2 infection. We found that DMPA treatment in mice decreased expression of the IL-36 cytokines in the FRT, while β-estradiol treatment increased expression. To evaluate the impact of IL-36γ on HSV-2 pathogenesis, we used an intravaginal challenge model and treated mice with DMPA to enhance susceptibility to infection. Mice treated with IL-36γ 4h prior to lethal challenge exhibited a delay in disease onset, less severe disease, decreased vaginal viral replication, increased disease resolution and overall survival. IL-36γ treatment increased levels of pro-inflammatory cytokines in vaginal lavages 4h after treatment, and neutrophil recruitment was enhanced and corresponded with increased levels of chemokines. Together, we demonstrate that IL-36γ is hormonally regulated in the FRT and that treatment with IL-36γ promotes the transient induction of immune mediators and neutrophil recruitment in the vaginal microenvironment that result in increased HSV-2 clearance.

Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses

Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease. Reported here, twenty-one female Hartley guinea pigs received intramuscular injection with either the VC2 vaccine, or equal volume of conditioned tissue culture media. Animals received 2 booster vaccinations at 21 day intervals following the initial vaccination. After vaccination, animals were challenged with the highly virulent HSV-2 (G) strain. Histologically, VC2 vaccinated animals had little to no apparent inflammation/disease following challenge. Unvaccinated animals developed moderate to severe erosive and ulcerative vaginitis. Quantitative reverse-transcriptase PCR analysis in VC2 vaccinated and challenged animals identified transcriptional signatures of Th17 and regulatory Tr1 cells associated with the inflammatory response primed by VC2 vaccination. Treatment of cultured human vaginal epithelial cells (VK2 cells) with a combination of IL-17A and IL-22 resulted in the significant induction of beta-defensin 3 expression. Further, treatment of VK2 cells with IL-17A, IL-22, IL-36 or beta-defensin 3 resulted in diminished HSV-2 replication. Overall, these results suggest that intramuscular vaccination with the live-attenuated vaccine VC2 primes a mucosal immune response predisposing the adaptive expression of transcripts associated with a Th17 response to challenge and these responses contribute to antiviral immunity.

Transcriptional Analysis of the Guinea Pig Mucosal Immune Response to Intravaginal Infection with Herpes Simplex Virus Type 2

Genital herpes infection in guinea pigs closely models human infection but tools for immune characterization are limited. Immunity to HSV infection at the vaginal epithelial surface was characterized in guinea pigs using PCR-based array analysis of vaginal swab samples. IFNγ was one of the most significantly upregulated genes throughout the infection and over 40% of genes with significantly altered expression were linked to IFNγ based on INTERFEROME analysis. IFNγ transcripts and biologically active IFNγ at the genital mucosa were confirmed by RTPCR and IFNγ reporter cells. Gene ontology analysis revealed activation of many biological processes related to genital immunity shared by humans and mice demonstrating the similarities of the local immune response to primary genital HSV-2 infection in guinea pigs and other established models. This transcription-based array will be useful for dissection of immunity during reactivation from latency, an infection outcome that is not well recapitulated by other animal models.

The effect of hormonal contraception and menstrual cycle timing on genital herpes simplex virus-2 shedding and lesions

Background The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. Methods We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use. Results In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03-1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66). Conclusions In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition

ObjectivesHerpes simplex virus type 2 (HSV-2) is a prevalent infection with great variability in clinical and virological manifestations among individuals. This prospective cohort study aims to evaluate the natural history...

GENITAL HERPES AND PREGNANCY

Herpes simplex virus of two types - HSV-1 and HSV-2, which can manifest as a primary and recurrent infection is the etiological factor of genital herpes. Herpes simplex virus is one of the most common sexually transmitted infections, in connection with which there is an increase in physical and psychological morbidity, which often remains an underestimated medical problem. With the vertical transmission of HSV during labor, diseases that are dangerous to the life and health in newborns can occur. Pregnant women with a primary infection of genital herpes belong to the high-risk group for the transmission of HSV to the newborn. Prophylaxis and prevention of vertical transmission of HSV are implemented in three directions: prevention of the recurrence of maternal genital HSV infection; prevention of transmission of the virus during pregnancy and childbirth; puerperal prophylaxis of the disease in a neonate infant born of a mother belonging to a high-risk group. This review focuses on such important aspects as laboratory diagnosis of HSV, antiviral therapy and prevention of viral infection during pregnancy, delivery and in the early neonatal period.

A model of genital herpes simplex virus Type 1 infection in Rhesus Macaques.

Although HSV-2 is the major cause of genital lesions, HSV-1 accounts for half of new cases in developed countries. Three healthy SHIV-SF162P3-infected Indian rhesus macaques were inoculated with 4×108 pfu of HSV-1 twice, with the second inoculation performed after the vaginal mucosa was gently abraded with a cytobrush. HSV-1 DNA was detected in vaginal swabs 5days after the second but not the first inoculation in all three macaques. An increase in inflammatory cytokines was detected in the vaginal fluids of the animals with no or intermittent shedding. Higher frequency of blood α4 β7high CD4+ T cells was measured in the animals with consistent and intermitted shedding, while a decrease in the frequency of CD69+ CD4+ T cells was present in all animals. This macaque model of genital HSV-1 could be useful to study the impact of the growing epidemic of genital HSV-1 on HIV infection.