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Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies—including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites—are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2's pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus-2 (HSV-2) is known to cause genital herpes a well-characterized sexually transmitted disease among humans. Although there are a couple of antiviral drugs available, poor adherence toward the treatment makes it more complicated. Recent reports on HSV drug resistance due to mutations have paved the way for the search of new antivirals required to control rising new virus infections. Objectives: The objective of this study was to screen the antiviral property of Coccinia indica ethanolic leaf extracts over the HSV-2 strain. Subjects and Methods: C. indica ethanolic extracts were assessed for anti-HSV-2 properties by the standard in vitro microtissue culture assay. Results: The results presented the least concentration of 75 µg of C. indica ethanolic leaf extract inhibited 100% of HSV-2 propagation and 50 µg inhibited around 60% of virus and showed a residual titer of 1008 ± 004 at day 5. Conclusion: The C. indica ethanolic extracts exhibited a significant antiviral activity against the HSV-2 virus in vitro. [ABSTRACT FROM AUTHOR]

Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies—including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites—are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2’s pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways.

Introduction: Spontaneous abortion (miscarriage) is one of extreme generic gestation complications. Yonder numerous causes leading to miscarriage like reproductive anatomical anomalies, genetic agents and virus infections in which viral infections, the infection with herpes simplex virus (HSV-2) is utmost common virus the occurs in the worldwide distribution. Aims: The objective of the study is to research the seroprevalence of Herpes simplex virus-2 in aborted women and detect the rate of interleukin-10 and HLA-G in the serum of aborted women compared with healthy pregnant women. Methods: One hundred and twenty which include 60 aborted women and 60 healthy pregnant women as a control group, the age of both groups are (15-43 years range). The blood samples are taken from both groups; the serum was separated and tested by ELISA to the detection of HSV-2 IgM, interleukin-10 & HLA-G. Results: Among aborted women most HSV-2 IgM antibody occur in age groups 21-30 &more than 30 years with rate 26(100.0%)&28(100.0%). There was a significant relation between IgM and cases in all ages (P=0.005). There was a significant relation with Pvalue=0.005 between IL-10 and cases and between sHLA-G and cases. Conclusion: IL-10 was increased in aborted women carrier with HSV-2 but the soluble HLA-G molecules are lowered in aborted women having HSV-2 infection. [ABSTRACT FROM AUTHOR]

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BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

Background: The incidence of sexually transmitted infections (STIs) has been noted to vary dramatically between population groups and over time. Here, the hypothesis that changes in network connectivity underpin these changes is explored. Methods: The incidence/prevalence estimates of HIV, herpes simplex virus-2, syphilis, chlamydia, and gonorrhoea, as well as two markers of sexual network connectivity (partner concurrency and multiple partnering) by ethnic group and sexual orientation in Kenya, South Africa, the United Kingdom (UK) and the United States (USA) were extracted from published studies. Pearson’s correlation was used to test the association between the markers of network connectivity and the incidence/prevalence of these five STIs. A literature review was performed to evaluate the possible causes of the increases and decreases in syphilis incidence over the past 60 years. Results: In each country, the five STIs were found to cluster in particular ethnic groups and sexual orientations and to be positively associated with the two markers of network connectivity. Syphilis incidence in the UK and USA was found to increase dramatically in the 1960s/1970s, decline in the 1980s and again increase in the late 1990s. These changes took place predominantly in men who have sex with men, and were preceded by corresponding changes in network connectivity. The large decline in antenatal syphilis prevalence in Kenya and South Africa in the 1990s were likewise preceded by declines in network connectivity. Conclusions: Although other explanatory variables are not controlled for, the present analysis is compatible with the hypothesis that differential network connectivity is a parsimonious explanation for variations in STI incidence over time and between populations.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

To retrospectively review the clinical characteristics of patients with herpes simplex virus type 2 (HSV-2) blepharokeratoconjunctivitis. Laboratory-proven HSV-2 blepharokeratoconjunctivitis cases were reviewed between 1995 and 2021. Ten of 725 (1.4%) patients had HSV-2 infection. Data were available for nine patients. Associated conditions included neonatal herpes (1/9, 11%), severe atopy (1/9, 11%), genital herpes (2/9, 22%), and systemic immune disorders (2/9, 22%). The most common presenting finding was pain and blurred vision (55.5%). Two patients (22%) had dendritic lesions and one patient (11%) had reduced corneal sensation. Complete resolution was reported in four patients (44.5%). Recurrence was noted in four patients (44.5%) despite antiviral prophylaxis. Corneal complications included scarring and neovascularization. The visual acuity at the last follow-up was 20/40 or worse in four patients (44.5%). HSV-2 is an uncommon cause of keratitis. Dendrites and loss of corneal sensation were uncommon. Recurrence was noted despite antiviral prophylaxis. [ABSTRACT FROM AUTHOR]

BackgroundFew cases concerning acute retinal necrosis with viral encephalitis in children have been reported, especially cases where the fundus cannot be identified due to severe vitreous opacity in the early stage that makes diagnosis difficult.MethodsWe conducted a retrospective review of an unusual case of herpes simplex virus-2 (HSV-2) acute retinal necrosis with viral encephalitis in an immunocompetent child, along with a review of relevant literature published up to September 2021.ResultAn 11-year-old girl presented with an approximate 20-day history of ocular redness and decreased visual acuity in the left eye. Examination revealed anterior uveitis and vitreous opacity in the left eye. An anterior chamber tap was performed because the fundus could not be observed clearly, and the aqueous humor was positive for HSV-2 DNA. Cerebrospinal fluid also tested positive for HSV-2. She was diagnosed with acute retinal necrosis syndrome and viral encephalitis. The condition was controlled with timely antiviral and steroid therapy. She was also treated with prophylactic laser therapy to prevent retinal detachment during subsequent follow-up. The pathogenesis, diagnosis, and treatment of HSV-2 acute retinal necrosis in children and the association between acute retinal necrosis and viral encephalitis are further discussed, based on published literature.ConclusionHSV-2-related pediatric acute retinal necrosis may be due to the acquisition of subclinical infection with HSV-2 during parturition, followed by reactivation of the virus latent in the body on account of certain factors. Moreover, it may be complicated with viral encephalitis. For suspected cases with invisible fundus, early intraocular fluid examination is especially helpful for differential diagnosis. Early diagnosis, early treatment, and timely prophylactic laser treatment to prevent retinal detachment are key to a better prognosis. Physicians need to pay attention to such suspected cases during diagnosis and treatment.

Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs’ coinfections and calls for further investigation with larger cohorts.

A 4 year-old girl developed bilateral acute retinal necrosis. She was treated, but lost vision in one eye. She had a recurrence 10 years later that was difficult to get under control. She was placed on antiviral prophylaxis and had no recurrence for 10 years until she stopped the prophylaxis. Purpose: To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism. Method: Case report. Results: A 4-year-old girl presented elsewhere with bilateral ARN, was treated, but developed a retinal detachment in the left eye that failed vitrectomy surgery. She was referred 10 years later with recurrent ARN. The infection was difficult to get under control, but eventually responded to intravenous acyclovir and foscarnet. She was given laser photocoagulation. She was placed on oral valacyclovir prophylaxis and was disease-free for 10 years at which point she decided to go to South America on vacation and stop her valacyclovir. Within a few days she developed a recurrence of ARN and flew back for treatment. She had discrete areas of retinal necrosis, vasculitis, and the laser photocoagulation lesions seemed to be ringed by a retinal change suggestive of retinitis. She responded to antiviral treatment, but developed a retinal detachment that was successfully treated. Her visual acuity was 20/20 six years later, and she was using antiviral prophylaxis. Conclusion: Recurrent ARN can respond to aggressive treatment. Chorioretinal scars, such as from photocoagulation, may be potential sites of viral invasion during recurrences. Antiviral prophylaxis may be indicated for at-risk patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of sexually transmitted infections (STIs) has been noted to vary dramatically between population groups and over time. Here, the hypothesis that changes in network connectivity underpin these changes is explored. Methods: The incidence/prevalence estimates of HIV, herpes simplex virus-2, syphilis, chlamydia, and gonorrhoea, as well as two markers of sexual network connectivity (partner concurrency and multiple partnering) by ethnic group and sexual orientation in Kenya, South Africa, the United Kingdom (UK) and the United States (USA) were extracted from published studies. Pearson’s correlation was used to test the association between the markers of network connectivity and the incidence/prevalence of these five STIs. A literature review was performed to evaluate the possible causes of the increases and decreases in syphilis incidence over the past 60 years. Results: In each country, the five STIs were found to cluster in particular ethnic groups and sexual orientations and to be positively associated with the two markers of network connectivity. Syphilis incidence in the UK and USA was found to increase dramatically in the 1960s/1970s, decline in the 1980s and again increase in the late 1990s. These changes took place predominantly in men who have sex with men, and were preceded by corresponding changes in network connectivity. The large decline in antenatal syphilis prevalence in Kenya and South Africa in the 1990s were likewise preceded by declines in network connectivity. Conclusions: Although other explanatory variables are not controlled for, the present analysis is compatible with the hypothesis that differential network connectivity is a parsimonious explanation for variations in STI incidence over time and between populations.

BACKGROUND: Herpes simplex virus (HSV) infection is associated with an increased risk of both human immune deficiency virus (HIV) transmission and acquisition. However, in India, literature on HSV infections in in HIV-infected males has been scarce. The present study was carried out to assess the seroprevalence of these viruses in HIV-infected males, so as to provide a baseline data from India and report on HSV associated GUD prevalence in HIV infected males. OBJECTIVE: The aim of the study was to estimate the seroprevalence of herpes simplex type 1 and 2 viruses in HIV-infected males with and without genital ulcers disease (GUD). MATERIAL AND METHODS: It was a prospective study. We included a total of 351 male participants in this study. Among these 233 were HIV-infected and 118 HIV-uninfected males who served as controls. The seroprevalence was estimated, using HSV-1 and 2 type specific IgG and IgM antibodies by ELISA. RESULTS: HIV-infected patients had a median age of 32 ± 6.97 years (interquartile range: 28–36). Of the 351 males, 25.92% (91/351) were infected with HSV-1 and HSV-2 both. The overall seroprevalence of HSV-1 singly infected, HSV-2 singly infected, and dual infection in HIV-infected males was 39.92%, 25.58%, and 37.33% whereas in HIV-uninfected group the corresponding figures were 71.18%, 5.08%, and 3.38%, respectively. Seven of 233 (3%) HIV-infected males were having incident HSV infection. GUD was reported in both HSV-1 and HSV-2 seropositive individuals. CONCLUSIONS: Both HSV-1 and HSV-2 infections were found to be associated with GUD in HIV-infected patients. The prevalence of HIV-HSV co-infection among GUD patients is high.

Currently there is a lack of data on herpes simplex virus-2 (HSV-2) and human immunodeficiency virus-1 (HIV-1) co-infections as well as risk factors for infection in antenatal women from South Africa. The present study attempts to fill this gap. This cross-sectional study was conducted from April to August 2017 at the antenatal clinic of the King Edward VIII hospital in Durban, South Africa. In total 248 pregnant women participated in the study. Data on the women’s demographics, sexual behaviour and clinical information were collected. HIV testing was conducted using a rapid test and the HerpeSelect 2 ELISA was used to test for HSV-2. The prevalence of HSV-2 and HIV-1 was 71% and 50% and coinfection rate was 60%. In adjusted analyses, women who were aged ≥ 35 years (adjusted odds ratio [AOR]: 4.95, p = 0.01), experienced recent symptoms of genital itching/sores/warts (AOR 2.48, p = 0.05) and were HIV-positive (AOR 3.64, p0.01), were more likely to be infected with HSV-2. Older age (30–34 years old) (AOR 6.53, p 0.01) and having ≥ 4 lifetime sex partners (AOR 4.59, p = 0.03) were strongly associated with HSV-2/HIV-1 co-infections. The findings of this study call for continuous risk reduction counselling in this population.

Objective: Assessing the epidemiological association between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in the United States, and characterizing the trends in the standardized HSV-1 and HSV-2 antibody prevalences (seroprevalences), 1999–2016. Methods: Source of data was the cross-sectional and nationally-representative biennial surveys of the National Health and Nutrition Examination Survey (NHANES). All nine NHANES rounds for 1999–2016 were included in analysis. Datasets of these rounds were combined and analyzed accounting for survey design and applying weighting procedures. Logistic regressions were used to identify associations with seropositivity. Sensitivity analyses were conducted. Results: Odds of HSV-1 infection declined by 2.84% (95% CI: 1.70%-4.00%) annually among men, and by 2.22% (95% CI: 1.23%-3.21%) among women. Declines were highest at younger ages. Odds of HSV-2 infection declined by 2.23% (95% CI: 0.71%-3.82%) annually among men, and by 2.89% (95% CI: 1.57%-4.28%) among women. Odds ratio of the association between HSV-2 and HSV-1 seropositivity was 0.71 (95% CI: 0.60–0.84) for men and 0.81 (95% CI: 0.72–0.91) for women, after adjustment for age, ethnicity, and year. Conclusion: HSV-1 and HSV-2 seroprevalences showed a strong declining trend for at least two decades, for both sexes and for the different ethnicities, possibly reflecting improvements in hygiene and living conditions (for HSV-1), and safer sexual behavior (for HSV-2). HSV-1 seroprevalence declines are most pronounced among young individuals. There is evidence for cross protection between the two infections, suggestive of HSV-1 seropositivity being partially protective against HSV-2 infection. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

Background: HIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART). Methods: We followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (<150 copies/mL) and low PVL (<1,000 copies/mL) between the cohorts using bootstrap methods and exact Poisson regression. Results: We evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up. Discussion: We observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples. [ABSTRACT FROM AUTHOR]

Introduction: Herpes simplex virus infection is one of the most common human infections in most parts of the world. Infection of female genitalia, as a common involving region in body, may cause neonatal infection to vitus and lead to dangerous complications. The aim of the current research was the assessment of the seroepidemiology of herpes simplex virus (HSV) in females referring to genetic center of Shahid Beheshti hospital in Hamadan from 2005 to 2010. Methods: In this retrospective descriptive study, from total of 5700 females, referring to the genetic center of ShahidBeheshti Hospital in Hamadan between 2005-2009, 921 females who their medical data of HSV tests were available in their records were studied. The collected data were analyzed using Chi square test, univariate and multivariate logistic regression models and SPSS version 16 software. Results: The results showed that 5.3% of the females referring to genetic center of Shahid Beheshti Hospital of hamadn were seropositive for hsv-2 antibody. The trend for change in prevalence of seropostivity of HSV 2 was significant and there was a meaningful relationship between marriage status and positivity of Hsv2 antibody among females. Conclusion: It seems that the prevalence of HSV-2 infection has had a decreased trend in recent years. The prevalence rate of HSV-2 was in consistent with other parts of the country, which may be due to the awareness of people of transmission routs, prevention as well as treatment methods.

Herpes Simplex Virus type 2 (HSV-2) is a neurotropic human pathogen. Upon de novo infection, the viral infected cell protein 0 (ICP0) is immediately expressed and interacts with various cellular components during the viral replication cycle. ICP0 is a multifunctional regulatory protein that has been shown to be important for both efficient viral replication and virus reactivation from latency. In particular, as previously demonstrated in transfected tissue culture models, ICP0 interacts with the cellular E3 ubiquitin ligase SIAH-1, which targets ICP0 for proteasomal degradation. However, the consequence of this virus-host interaction during the establishment of HSV-2 infection in vivo has not yet been elucidated. Here we confirmed that ICP0 of HSV-2 interacts with SIAH-1 via two conserved PxAxVxP amino acid binding motifs. We also demonstrate in vitro that a SIAH-1 binding-deficient HSV-2 strain, constructed by homologous recombination technology, exhibits an attenuated growth curve and impaired DNA and protein synthesis. This attenuated phenotype was also confirmed in an in vivo ocular infection mouse model. Specifically, viral load of the SIAH-1 binding-deficient HSV-2 mutant was significantly reduced in the trigeminal ganglia and brain stem at day 5 and 7 post infection. Our findings indicate that the interplay between ICP0 and SIAH-1 is important for efficient HSV-2 replication in vivo, thereby affecting viral dissemination kinetics in newly infected organisms, and possibly revealing novel targets for antiviral therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Herpes simplex virus (HSV) infection is associated with an increased risk of both human immune deficiency virus (HIV) transmission and acquisition. However, in India, literature on HSV infections in in HIV-infected males has been scarce. The present study was carried out to assess the seroprevalence of these viruses in HIV-infected males, so as to provide a baseline data from India and report on HSV associated GUD prevalence in HIV infected males. OBJECTIVE: The aim of the study was to estimate the seroprevalence of herpes simplex type 1 and 2 viruses in HIV-infected males with and without genital ulcers disease (GUD). MATERIAL AND METHODS: It was a prospective study. We included a total of 351 male participants in this study. Among these 233 were HIV-infected and 118 HIV-uninfected males who served as controls. The seroprevalence was estimated, using HSV-1 and 2 type specific IgG and IgM antibodies by ELISA. RESULTS: HIV-infected patients had a median age of 32 ± 6.97 years (interquartile range: 28–36). Of the 351 males, 25.92% (91/351) were infected with HSV-1 and HSV-2 both. The overall seroprevalence of HSV-1 singly infected, HSV-2 singly infected, and dual infection in HIV-infected males was 39.92%, 25.58%, and 37.33% whereas in HIV-uninfected group the corresponding figures were 71.18%, 5.08%, and 3.38%, respectively. Seven of 233 (3%) HIV-infected males were having incident HSV infection. GUD was reported in both HSV-1 and HSV-2 seropositive individuals. CONCLUSIONS: Both HSV-1 and HSV-2 infections were found to be associated with GUD in HIV-infected patients. The prevalence of HIV-HSV co-infection among GUD patients is high. [ABSTRACT FROM AUTHOR]

Patients with Herpes Simplex Virus-2 (HSV-2) infection face a significantly higher risk of contracting HIV-1. This is thought to be due to herpetic lesions serving as entry points for HIV-1 and tissue-resident CD4+ T cell counts increasing during HSV-2 lesional events. We have created a stochastic and spatial mathematical model describing the dynamics of HSV-2 infection and immune response in the genital mucosa. Using our model, we first study the dynamics of a developing HSV-2 lesion. We then use our model to quantify the risk of infection with HIV-1 following sexual exposure in HSV-2 positive women. Untreated, we find that HSV-2 infected women are up to 8.6 times more likely to acquire HIV-1 than healthy patients. However, when including the effects of the HSV-2 antival drug, pritelivir, the risk of HIV-1 infection is predicted to decrease by up to 35%, depending on drug dosage. We estimate the relative importance of decreased tissue damage versus decreased CD4+ cell presence in determining the effectiveness of pritelivir in reducing HIV-1 infection. Our results suggest that clinical trials should be performed to evaluate the effectiveness of pritelivir or similar agents in preventing HIV-1 infection in HSV-2 positive women. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence varies from 1.7% to 14.8% between ethnic groups in Uganda. Understanding the factors responsible for this heterogeneity in HIV spread may guide prevention efforts. Methods: We evaluated the relationship between HIV prevalence by ethnic group and a range of risk factors as well as the prevalence of herpes simplex virus-2 (HSV-2), syphilis and symptomatic STIs in the 2004/2005 Uganda HIV/AIDS Sero-Behavioural Survey—a two stage, nationally representative, population based survey of 15–59-year-olds. Spearman’s correlation was used to assess the relationship between HIV prevalence and each variable. Results: There was a positive association between HIV prevalence and HSV-2, symptomatic STIs and high-risk sex (sex with a non-cohabiting, non-marital partner) for women. Non-significant positive associations were present between HIV and high-risk sex for men and lifetime number of partners for men and women. Conclusion: Variation in sexual behavior may contribute to the variations in HIV, HSV-2 and other STI prevalence by ethnic group in Uganda. Further work is necessary to delineate which combinations of risk factors determine differential STI spread in Uganda. [ABSTRACT FROM AUTHOR]

Background: In South Africa, treatment of genital ulcer disease (GUD) occurs in the context of syndromic management. GUD aetiological studies have been conducted in Johannesburg since 2007. We report on GUD pathogen prevalence, sero-prevalence of STI co-infections and aetiological trends among GUD patients presenting to a community-based primary healthcare facility in Johannesburg over a 9-year period. Methods and findings: GUD surveys were conducted from January to April each year. Consecutive genital ulcers were sampled from consenting adults. Swab-extracted DNA was tested by multiplex real-time PCR assays for herpes simplex virus (HSV), Treponema pallidum (TP), Haemophilus ducreyi (HD) and Chlamydia trachomatis (CT). HSV-positive DNA extracts were further subtyped into HSV-1 and HSV-2 using a commercial PCR assay; CT-positive extracts were tested with an in-house PCR assay specific for serovars L1-L3 (lymphogranuloma venereum). Sera were tested for HIV, HSV-2, and syphilis co-infections. Giemsa-stained ulcer smears were screened for Klebsiella granulomatis by microscopy. Data were analysed with STATATM version 14. Of 771 GUD specimens, 503 (65.2%) had a detectable pathogen: HSV 468 (60.7%); TP 30 (3.9%); CT L1-3 7 (0.9%); HD 4 (0.5%). No aetiological agents were detected in 270 (34.8%) ulcer specimens. Seroprevalence rates were as follows: HIV 61.7%; HSV-2 80.2% and syphilis 5.8%. There was a strong association between GUD pathogen detection and HIV seropositivity (p < 0.001); 68% of cases caused by HSV were co-infected with HIV. There was a significant decline in the relative prevalence of ulcer-derived HSV over time, predominantly from 2013–2015 (p-value for trend = 0.023); and a trend towards a decrease in the HIV seropositivity rate (p-value for trend = 0.209). Conclusions: HSV remains the leading cause of pathogen-detectable GUD in South Africa. The prevalence of HIV co-infection among GUD patients is high, underlining the importance of linkage to universal HIV testing and treatment in primary healthcare settings. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) comprise a significant portion of the infectious-disease burden among rural people in the Global South. Particular characteristics of ruralness—low-density settlements and poor infrastructure—make healthcare provision difficult, and remoteness, typically a characteristic of ruralness, often compounds the difficultly. Remoteness may also accelerate STI transmission, particularly that of viral STIs, through formation of small, highly connected sexual networks through which pathogens can spread rapidly, especially when partner concurrency is broadly accepted. Herein, we explored the effect of remoteness on herpes simplex virus type-2 (HSV-2) epidemiology among semi-nomadic pastoralists in northwestern (Kaokoveld) Namibia, where, in 2009 we collected HSV-2-specific antibody status, demographic, sexual network, and travel data from 446 subjects (women = 213, men = 233) in a cross-sectional study design. HSV-2 prevalence was high overall in Kaokoveld (>35%), but was heterogeneously distributed across locally defined residential regions: some regions had significantly higher HSV-2 prevalence (39–48%) than others (21–33%). Using log-linear models, we asked the following questions: 1) Are sexual contacts among people in high HSV-2-prevalence regions more likely to be homophilous (i.e., from the same region) than those among people from low-prevalence regions? 2) Are high-prevalence regions more “functionally” remote, in that people from those regions are more likely to travel within their own region than outside, compared to people from other regions? We found that high-prevalence regions were more sexually homophilous than low-prevalence regions and that those regions also had higher rates of within-region travel than the other regions. These findings indicate that remoteness can create contact structures for accelerated STI transmission among people who are already disproportionately vulnerable to consequences of untreated STIs. [ABSTRACT FROM AUTHOR]

Background: Quantitative estimation of the extent to which the immune system's protective effect against one herpes simplex virus type 2 (HSV-2) infection protects against infection with additional HSV-2 strains is important for understanding the potential for HSV-2 vaccine development. Using viral genotyping, we estimated the prevalence of HSV-2 dual-strain infection and identified risk factors.Methods and Findings: People with and without HIV infection participating in HSV-2 natural history studies (University of Washington Virology Research Clinic) and HIV prevention trials (HIV Prevention Trials Network 039 and Partners in Prevention HSV/HIV Transmission Study) in the US, Africa, and Peru with 2 genital specimens each containing ≥105 copies herpes simplex virus DNA/ml collected a median of 5 months apart (IQR: 2-11 months) were included. It is unlikely that 2 strains would be detected in the same sample simultaneously; therefore, 2 samples were required to detect dual-strain infection. We identified 85 HSV-2 SNPs that, in aggregate, could determine whether paired HSV-2 strains were the same or different with >90% probability. These SNPs were then used to create a customized high-throughput array-based genotyping assay. Participants were considered to be infected with more than 1 strain of HSV-2 if their samples differed by ≥5 SNPs between the paired samples, and dual-strain infection was confirmed using high-throughput sequencing (HTS). We genotyped pairs of genital specimens from 459 people; 213 (46%) were men, the median age was 34 years (IQR: 27-44), and 130 (28%) were HIV seropositive. Overall, 272 (59%) people were from the US, 59 (13%) were from Peru, and 128 (28%) were from 8 countries in Africa. Of the 459 people, 18 (3.9%) met the criteria for dual-strain infection. HTS and phylogenetic analysis of paired specimens confirmed shedding of 2 distinct HSV-2 strains collected at different times in 17 pairs, giving an estimated dual-strain infection prevalence of 3.7% (95% CI = 2.0%-5.4%). Paired samples with dual-strain infection differed by a median of 274 SNPs in the UL_US region (range 129-413). Matching our observed dual-strain infection frequency to simulated data of varying prevalences and allowing only 2 samples per person, we inferred the true prevalence of dual-strain infection to be 7%. In multivariable analysis, controlling for HIV status and continent of origin, people from Africa had a higher risk for dual-strain infection (risk ratio [RR] = 9.20, 95% CI = 2.05-41.32), as did people who were HIV seropositive (RR = 4.06, 95% CI = 1.42-11.56).Conclusions: HSV-2 dual-strain infection was detected in 3.7% of paired samples from individual participants, and was more frequent among people with HIV infection. Simulations suggest that the true prevalence of dual-strain infection is 7%. Our data indicate that naturally occurring immunity to HSV-2 may be protective against infection with a second strain. This study is limited by the inability to determine the timing of acquisition of the second strain. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future. [ABSTRACT FROM AUTHOR]

While HSV-2 typically causes genital lesions, HSV-1 is increasingly the cause of genital herpes. In addition, neonatal HSV infections are associated with a high rate of mortality and HSV-2 may increase the risk for HIV or Zika infections, reinforcing the need to develop an effective vaccine. In the GSK Herpevac trial, doubly sero-negative women were vaccinated with a truncated form of gD2 [gD2(284t)], then examined for anti-gD serum titers and clinical manifestations of disease. Surprisingly, few vaccinees were protected against genital HSV-2 but 86% were protected from genital HSV-1. These observations suggest that subtle differences in gD structure might influence a protective response. To better understand the antigenic structure of gD and how it impacts a protective response, we previously utilized several key anti-gD monoclonal antibodies (mAbs) to dissect epitopes in vaccinee sera. Several correlations were observed but the methodology limited the number of sera and mAbs that could be tested. Here, we used array-based surface plasmon imaging (SPRi) to simultaneously measure a larger number of protein-protein interactions. We carried out cross-competition or “epitope binning” studies with 39 anti-gD mAbs and four soluble forms of gD, including a form [gD2(285t)] that resembles the Herpevac antigen. The results from these experiments allowed us to organize the mAbs into four epitope communities. Notably, relationships within and between communities differed depending on the form of gD, and off-rate analysis suggested differences in mAb-gD avidity depending on the gD serotype and length. Together, these results show that gD1 and gD2 differ in their structural topography. Consistent with the Herpevac results, several mAbs that bind both gD1 and gD2 neutralize only HSV-1. Thus, this technology provides new insights into the antigenic structure of gD and provides a rationale as to how vaccination with a gD2 subunit may lead to protection from HSV-1 infection. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus type 2 (HSV-2) infections are associated with increased risk of HIV transmission. We determined HSV-2 prevalence, incidence and associated risk factors, incidence among persons with indeterminate results, and prevalence of HSV-2/HIV co-infection among young adults (18–34 years) and adolescents (16–17 years) enrolled in an HIV incidence cohort study in western Kenya. Methods: Participants (n = 1106; 846 adults) were screened and those HIV-1 negative were enrolled and followed-up quarterly for one year. HSV-2 was assessed using the Kalon enzyme immunoassay. HSV-2 incidence was calculated separately among HSV-2 seronegative participants and those indeterminate at baseline. Logistic regression was used to estimate the odds of HSV-2 infection and Poisson regression was used to assess HSV-2 incidence and associated factors. Results: Overall, HSV-2 prevalence was 26.6% [95% confidence interval (CI): 23.9–29.4] and was higher in adults (31.5% [95% CI: 28.3–34.9]) than adolescents (10.7% [95% CI: 7.1–15.3]). Factors associated with prevalent HSV-2 included female gender, increasing age, HIV infection, history of sexually transmitted infection, low level of education, multiple sexual partners, and being married, divorced, separated or widowed. Overall HSV-2 incidence was 4.0 per 100 person-years (/100PY) 95% CI: 2.7–6.1 and was higher in adults (4.5/100PY) and females (5.1/100PY). In multivariable analysis only marital status was associated with HSV-2 incidence. Among 45 participants with indeterminate HSV-2 results at baseline, 22 seroconverted, resulting in an incidence rate of 53.2 /100PY [95% CI: 35.1–80.9]. Inclusion of indeterminate results almost doubled the overall incidence rate to 7.8 /100 PY [95% CI: 5.9–10.5]. Prevalence of HIV/HSV-2 co-infection was higher in female adults than female adolescents (17.1 [95% CI: 13.6–21.0] versus 3.4 [95% CI: 1.1–7.8]). Conclusion: The high incidence rate among persons with indeterminate results underscores the public health concerns for HSV-2 spread and underreporting of the HSV-2 burden. Careful consideration is needed when interpreting HSV-2 serology results in these settings. [ABSTRACT FROM AUTHOR]

Background: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144. Methods: Of the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66 to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected. Conclusions: AIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies. [ABSTRACT FROM AUTHOR]

Salvia desoleana Atzei & V. Picci is an indigenous species in Sardinia island used in folk medicine to treat menstrual, digestive and central nervous system diseases. Nowadays, it is widely cultivated for the pleasant smell of its essential oil (EO), whose antimicrobial and antifungal activities have already been screened. This study evaluated the in vitro anti-Herpes Simplex Virus-2 (HSV-2) activity of S. desoleana EO, fractions and main components: linalyl acetate, alpha terpinyl acetate, and germacrene D. Phytochemical composition of S. desoleana EO was studied by GC-FID/MS analysis and the active fraction(s) and/or compounds in S. desoleana EO were identified with a bioassay-guided fractionation procedure through in vitro assays on cell viability and HSV-2 and RSV inhibition. S. desoleana EO inhibits both acyclovir sensitive and acyclovir resistant HSV-2 strains with EC50 values of 23.72 μg/ml for the former and 28.57 μg/ml for the latter. Moreover, a significant suppression of HSV-2 replication was observed with an EC50 value of 33.01 μg/ml (95% CI: 26.26 to 41.49) when the EO was added post-infection. Among the fractions resulting from flash column chromatography on silica gel, the one containing 54% of germacrene D showed a similar spectrum of activity of S. desoleana EO with a stronger suppression in post-infection stage. These results indicated that S. desoleana EO can be of interest to develop new and alternative anti-HSV-2 products active also against acyclovir-resistant HSV-2 strains. [ABSTRACT FROM AUTHOR]

Objectives: Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods: We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results: At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion: Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is an important factor that causes cervical cancer and non-melanoma skin cancer (NMSC), while HSV-2 plays an important role when HR-HPV triggers the cancer. Thus, a quick and convenient assay in the detection of HPV and HSV-2in the screening of HPV and HSV-2 infection is required. Two respective HPV and HSV-2 detection methods were established based on loop-mediated isothermal amplification (LAMP) assay. Specific outer primers, inner primers, and loop primers were designed according to the conserved domains of HPV and HSV-2 genomes, respectively, while degenerate primers were used for HPV assay. After optimizing the reaction conditions, the results were observed by LAMP Tubidimeter real-time LA-320. Standard plasmids HPV-L-P and HSV-2-L-P were cloned and used in sensitivity tests of HPV LAMP and HSV-2 LAMP, respectively. Fifty samples of actinic keratosis (AK), 20 samples of squamous cell carcinoma (SCC), 50 samples of basal cell carcinoma (BCC) and 20 samples of seborrheic keratosis (SK) were detected by HPV assay. Seventy three clinical samples of vaginitis, chronic cervicitis, cervical intraepithelial neoplasias and cervical cancer level positive were detected with HPV and HSV-2 assays. The reaction conditions of two assays were the same with a reaction temperature of 63 °C and a reaction time of 45 min. The sensitivity of HPV LAMP assay was 10 copies/μL, while that of the HSV-2 LAMP assay was 100 copies/μL. No cross-reactivity was observed. The HPV positive rates of AK, SCC, BCC and SK samples were 80% (40/50), 75% (15/20), 44% (22/50) and 21% (15/72), respectively. As an economic and quick diagnostic tool, LAMP assay is conducive to the extensive screening of HPV and HSV-2 and has huge potential to be promoted in resource-limited hospitals. [ABSTRACT FROM AUTHOR]

Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR–associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients. [ABSTRACT FROM AUTHOR]

A fully automated multiplex real-time PCR assay—including a sample process control and a plasmid based positive control—for the detection and differentiation of herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2) and varicella-zoster virus (VZV) from cerebrospinal fluids (CSF) was developed on the BD Max platform. Performance was compared to an established accredited multiplex real time PCR protocol utilizing the easyMAG and the LightCycler 480/II, both very common devices in viral molecular diagnostics. For clinical validation, 123 CSF specimens and 40 reference samples from national interlaboratory comparisons were examined with both methods, resulting in 97.6% and 100% concordance for CSF and reference samples, respectively. Utilizing the BD Max platform revealed sensitivities of 173 (CI 95%, 88–258) copies/ml for HSV1, 171 (CI 95%, 148–194) copies/ml for HSV2 and 84 (CI 95%, 5–163) copies/ml for VZV. Cross reactivity could be excluded by checking 25 common viral, bacterial and fungal human pathogens. Workflow analyses displayed shorter test duration as well as remarkable fewer and easier preparation steps with the potential to reduce error rates occurring when manually assessing patient samples. This protocol allows for a fully automated PCR assay on the BD Max platform for the simultaneously detection of herpesviridae from CSF specimens. Singular or multiple infections due to HSV1, HSV2 and VZV can reliably be differentiated with good sensitivities. Control parameters are included within the assay, thereby rendering its suitability for current quality management requirements. [ABSTRACT FROM AUTHOR]

The article discusses the interaction of the herpes simplex virus (HSV) with its host. Topics discussed include the entrance of the HSV into the sensory neurons for the establishment of a latency in neural ganglia, the viral proteins encoded by the HSV to encounter the innate response of the host to infection, and the required functions of γ34.5 for pathogenesis.

Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques), while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and Objectives: The present study was undertaken to determine Herpes Simplex Virus-2 seroprevalence in sexually active adults aged 20-49 and to investigate the correlation with sociodemographic characteristics and to find its association with other sexually transmitted diseases especially HIV and also to assess the proportion of primary and reactivated HSV-2 cases. Materials and Methods: This prospective study was carried out for a period of six months in a tertiary care hospital. Serum samples were taken from 91 patients attending the out Patient clinic of the Department of Venereology. The serological testing for HSV-2 was performed on all the specimens by using Euroimmun anti-HSV2 (gG2) IgM ELISA and IgG ELISA. Results: Out of the 91 STD patients in the study group, 18 males (34.62%) and 14 females (36.84%) tested positive for HSV-2 antibodies. Seropositivity rate is 35.16%. More number of HSV-2 positive cases were seen among males, older age, rural residence, low socioeconomic status, single marital status, irregular condom usage during the sexual intercourses with new partners and with higher number of sexual partners during lifetime. HSV-2 IgM alone was positive in three cases, HSV-2 IgG alone was positive in 26 cases and three had a positive HSV-2 IgM and IgG result. Addition of IgM testing increased rate of detecting seroconversion, 31.87%, when only IgG ELISA was used, to 35.16 % patients when IgM test was added. In the study group four cases tested positive for VDRL, and one of them was a known positive case. Among the 55 HIV positive cases in the study group, HSV 2 was positive in 17 cases and among the 36 HIV negative cases HSV 2 was positive in 15 cases. (30.91% and 47.22%).Though the number of HIV cases were high, HSV 2 positivity among them was statistically not significant. Conclusion:The purpose of screening for HSV-2 is not only to identify seropositivity, but to help seropositive people identify symptoms and protect themselves from acquiring HIV and to protect their partners and seronegative people from acquiring HSV-2 and/or HIV.

Background and Objectives: The present study was undertaken to determine Herpes Simplex Virus-2 seroprevalence in sexually active adults aged 20-49 and to investigate the correlation with sociodemographic characteristics and to find its association with other sexually transmitted diseases especially HIV and also to assess the proportion of primary and reactivated HSV-2 cases. Materials and Methods: This prospective study was carried out for a period of six months in a tertiary care hospital. Serum samples were taken from 91 patients attending the out Patient clinic of the Department of Venereology. The serological testing for HSV-2 was performed on all the specimens by using Euroimmun anti-HSV2 (gG2) IgM ELISA and IgG ELISA. Results: Out of the 91 STD patients in the study group, 18 males (34.62%) and 14 females (36.84%) tested positive for HSV-2 antibodies. Seropositivity rate is 35.16%. More number of HSV-2 positive cases were seen among males, older age, rural residence, low socioeconomic status, single marital status, irregular condom usage during the sexual intercourses with new partners and with higher number of sexual partners during lifetime. HSV-2 IgM alone was positive in three cases, HSV-2 IgG alone was positive in 26 cases and three had a positive HSV-2 IgM and IgG result. Addition of IgM testing increased rate of detecting seroconversion, 31.87%, when only IgG ELISA was used, to 35.16 % patients when IgM test was added. In the study group four cases tested positive for VDRL, and one of them was a known positive case. Among the 55 HIV positive cases in the study group, HSV 2 was positive in 17 cases and among the 36 HIV negative cases HSV 2 was positive in 15 cases. (30.91% and 47.22%).Though the number of HIV cases were high, HSV 2 positivity among them was statistically not significant. Conclusion:The purpose of screening for HSV-2 is not only to identify seropositivity, but to help seropositive people identify symptoms and protect themselves from acquiring HIV and to protect their partners and seronegative people from acquiring HSV-2 and/or HIV. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus type-1 (HSV-1) and type-2 (HSV-2) establish life-long infections and cause significant orofacial and genital infections in humans. HSV-1 is the leading cause of infectious blindness in the western world. Currently, there are no available vaccines to protect against herpes simplex infections. Recently, we showed that a single intramuscular immunization with an HSV-1(F) mutant virus lacking expression of the viral glycoprotein K (gK), which prevents the virus from entering into distal axons of ganglionic neurons, conferred significant protection against either virulent HSV-1(McKrae) or HSV-2(G) intravaginal challenge in mice. Specifically, 90% of the mice were protected against HSV-1(McKrae) challenge, while 70% of the mice were protected against HSV-2(G) challenge. We constructed the recombinant virus VC2 that contains specific mutations in gK and the membrane protein UL20 preventing virus entry into axonal compartments of neurons, while allowing efficient replication in cell culture, unlike the gK-null virus, which has a major defect in virus replication and spread. Intramuscular injection of mice with 107 VC2 plaque forming units did not cause any significant clinical disease in mice. A single intramuscular immunization with the VC2 virus protected 100% of mice against lethal intravaginal challenge with either HSV-1(McKrae) or HSV-2(G) viruses. Importantly, vaccination with VC2 produced robust cross protective humoral and cellular immunity that fully protected vaccinated mice against lethal disease. Quantitative PCR did not detect any viral DNA in ganglionic tissues of vaccinated mice, while unvaccinated mice contained high levels of viral DNA. The VC2 virus may serve as an efficient vaccine against both HSV-1 and HSV-2 infections, as well as a safe vector for the production of vaccines against other viral and bacterial pathogens. [ABSTRACT FROM AUTHOR]

Objectives: Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted disease, but there is limited data on its epidemiology among urban populations. The urban Emergency Department (ED) is a potential venue for surveillance as it predominantly serves an inner city minority population. We evaluate the seroprevalence and factors associated with HSV-2 infection among patients attending the Johns Hopkins Hospital Adult Emergency Department (JHH ED). Methods: An identity unlinked-serosurvey was conducted between 6/2007 and 9/2007 in the JHH ED; sera were tested by the Focus HerpeSelect ELISA. Prevalence risk ratios (PRR) were used to determine factors associated with HSV-2 infection. Results: Of 3,408 serum samples, 1,853 (54.4%) were seropositive for HSV-2. Females (adjPRR  = 1.47, 95% CI 1.38–1.56), non-Hispanic blacks (adjPRR  = 2.03, 95% CI 1.82–2.27), single (adjPRR  = 1.15, 95% CI 1.07–1.25), divorced (adjPRR  = 1.28, 95% CI 1.15–1.41), and unemployed patients (adjPRR  = 1.13, 95% CI 1.05–1.21) had significantly higher rates of HSV-2 infection. Though certain zip codes had significantly higher seroprevalence of HSV-2, this effect was completely attenuated when controlling for age and gender. Conclusions: Seroprevalence of HSV-2 in the JHH ED was higher than U.S. national estimates; however, factors associated with HSV-2 infection were similar. The high seroprevalence of HSV-2 in this urban ED highlights the need for targeted testing and treatment. Cross-sectional serosurveys in the urban ED may help to examine the epidemiology of HSV-2. [ABSTRACT FROM AUTHOR]

Background. Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions.Methods. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses.Results. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties.Conclusions. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2–mediated disease. [ABSTRACT FROM AUTHOR]