Genital Herpes Infection Research Articles

The Herpes Simplex Virus 2 UL21 Protein Is Essential for Virus Propagation

Herpes simplex virus 2 (HSV-2) is an important human pathogen that is the major cause of genital herpes infections and a significant contributor to the epidemic spread of human immunodeficiency virus infections. The UL21 gene is conserved throughout the Alphaherpesvirinae subfamily and encodes a tegument protein that is dispensable for HSV-1 and pseudorabies virus replication in cultured cells; however, its precise functions have not been determined. To investigate the role of UL21 in the HSV-2 replicative cycle, we constructed a UL21 deletion virus (HSV-2 ΔUL21) using an HSV-2 bacterial artificial chromosome, pYEbac373. HSV-2 ΔUL21 was unable to direct the production of infectious virus in noncomplementing cells, whereas the repaired HSV-2 ΔUL21 strain grew to wild-type (WT) titers, indicating that UL21 is essential for virus propagation. Cells infected with HSV-2 ΔUL21 demonstrated a 2-h delay in the kinetics of immediate early viral gene expression. However, this delay in gene expression was not responsible for the inability of cells infected with HSV-2 ΔUL21 to produce virus insofar as late viral gene products accumulated to WT levels by 24 h postinfection (hpi). Electron and fluorescence microscopy studies indicated that DNA-containing capsids formed in the nuclei of ΔUL21-infected cells, while significantly reduced numbers of capsids were located in the cytoplasm late in infection. Taken together, these data indicate that HSV-2 UL21 has an early function that facilitates viral gene expression as well as a late essential function that promotes the egress of capsids from the nucleus.

Herpes simplex virus type 2 serological testing at a community court: Predictors of test acceptance and seropositivity among female defendants

Despite the high prevalence of herpes simplex virus type 2 (HSV-2), testing for asymptomatic infections is uncommon. One population for whom targeted interventions may be prioritized include individuals involved with the correctional system. Here we describe the acceptability of a novel HSV-2 screening program, implemented in a court setting, as a possible intervention for corrections-involved women. Female defendants completed an interviewer administered survey assessing factors associated with uptake/refusal of free point-of-care HSV-2 serologic testing and HSV-2 seropositivity. Participants included 143 women, 18-62 years old (mean 32.85) with diverse ethnicities. The majority (65.7%) accepted testing and 62.4% tested HSV-2 seropositive. Factors independently associated with test acceptance included higher perceived susceptibility to genital herpes infection and not receiving a preventative health screen. Women who were seropositive tended to be older, Black, report having previous STI, and be arrested on a prostitution charge. Findings suggest point-of-care testing in a court setting is acceptable to women and can be implemented to improve case finding of STI.

Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.

Genital Herpes Beliefs: Implications for Sexual Health

Study ObjectiveGenital herpes (HSV) is exceedingly common in the United States and women are disproportionally affected. This study aims to describe young women's beliefs about HSV and examine the correlates of those beliefs. DesignA 40-item Herpes Representation measure (HSV-RoSTD) and a demographic questionnaire were administered to a convenience sample of young women. Data analysis included descriptive statistics, t-tests and Pearson's correlations. SettingFour women's health clinics and one large state university. Participants302 women aged 18-24 years. InterventionsNone. Main Outcome MeasuresFour dimensions of HSV representations (cause, identity, future perspective, and psychosocial consequences), age and STD testing history. ResultsNearly all (98%) believed that HSV would result in genital sores and 68% believed they could tell if their sexual partner had HSV. Most (89%) understood the longevity of HSV; however, 30% believed that they could take a pill to get rid of the infection, and 15% indicated that it was likely they would die from HSV. Negative beliefs about the psychosocial impact of HSV were common as 95% indicated they would be depressed and 90% indicated concern about sex and partner notification. Those who were younger and those who had never been tested for STDs believed a genital herpes infection is highly symptomatic. Finally, negative beliefs about the psychosocial consequences of HSV were associated with beliefs about HSV being symptomatic, having a negative impact on future health, and being associated with sexual risk behaviors. ConclusionsYoung women have misconceptions about HSV, particularly regarding the symptomatology and the role of HSV medication. Noteworthy concerns about the negative psychosocial consequences of an HSV diagnosis were also raised, all of which have implications for young women's sexual health.

Maternal and Neonatal Herpes Simplex Virus Infections

Genital herpes infections are extremely common worldwide and ~22% of pregnant women are infected with herpes simplex virus. Eighty percent of those affected with genital herpes are unaware of being infected. The most devastating consequence of maternal genital herpes is neonatal herpes disease. Fortunately, neonatal herpes simplex infections are uncommon but due to the morbidity and mortality associated with the infection are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction assay for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy have revolutionized the diagnosis and management of these infants. Most recently, the initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This review will summarize the epidemiology of maternal and neonatal herpes infections and discuss clinical presentation, diagnosis, management, and follow-up of infants with neonatal herpes disease.

Verrucous herpetic infection of the scrotum and the groin in an immuno-competent patient: Case report and review of the literature

Atypical presentations of genital herpes are more commonly described among immuno-compromised patients. Furthermore, verrucous lesions may be attributed to acyclovir resistant strains of herpes simplex virus as well as co-infection with fungi and other viruses in this patient population. We describe the first case of verrucous genital herpes infection in an immuno-competent patient.

Intranasal immunization in mice with non-ionic surfactants vesicles containing HSV immunogens: A preliminary study as possible vaccine against genital herpes

The purpose of this study was to investigate the potential of intranasal immunization with non-ionic surfactant vesicles (NISV) containing either the secretory recombinant form of glycoprotein B (gBs) of herpes simplex virus type 1 or a related polylysine reach peptides (DTK) for induction of protective immunity against genital herpes infection in mice. NISV were prepared by lipid film hydration method. The mean diameter of vesicles was around 390 nm for DTK-containing NISV (DTK-NISV) and 320 nm for gB1s-containing NISV (gB1s-NISV). The encapsulation efficiency of the molecules was comprised between 57% and 70%. After 7-14 day NISV maintained stable dimensions and a drug encapsulation higher than 48%. We showed that intranasal immunization with gB1s-NISV induces gB-specific IgG antibody and lymphoproliferative responses, whereas vaccination with DTK-NISV was not able to generate a gB-specific immune response. Our results indicate that vaccination of BALB/c mice with gB1s-NISV induced Th1 responses, as characterized by increased titre of IG2a in plasma and IFN-production in CD4+ splenic cells. Intranasal immunization with gB1s-NISV could elicit 90% (almost complete) protection against a heterologous lethal vaginal challenge with herpes simplex virus type 2. These data may have implications for the development of a mucosal vaccine against genital herpes.

Nasal and skin delivery of IC31®-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31® in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31® through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31®-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31®-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31® conferred 80–100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31® for induction of protective immunity against genital herpes and other sexually transmitted infections.

P80 Genitourinary medicine physicians need further training in the management of HSV in late pregnancy

BackgroundTransmission rates of neonatal herpes simplex virus (HSV) infection varies from 30% to 50% if shedding with primary infection during the third trimester of pregnancy, to <3% with active recurrent...

P97 Women requiring emergency contraception are a high risk group for sexually transmitted infections in future

BackgroundWomen in UK are able to get emergency hormonal contraception from various sources including general practice, community contraception clinic, A&E, pharmacies and GUM services. Other than the GUM services most...

Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection

The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD(50) inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine.

Sequencing and phylogenetic analysis of Herpes simplex virus type-2 gG gene in Iran

Herpes simplex virus type-2 (HSV-2) is the main cause of genital herpes infection. Its prevalence is increasing worldwide and varies widely with generally higher rate in developing than developed countries and urban than rural areas. Identification of glycoprotein G (gG-2) from HSV-2 as type-specific antigen have been helpful in development of reliable and accurate type-specific serological methods. For determination of the genetic relationship of HSV-2 glycoprotein G gene (gG) in Iran with those in other countries, DNA fragment of 1100 bp corresponding to gG from six HSV-2 strains have been isolated from human infected sera samples in Iran, it was amplified in PCR system and was sequenced for determining nucleotide sequence and compared with identified nucleotide sequence of this gene in other countries. The results indicated the presence of 0.3 to 9.5% variability in gG gene in six sequenced samples in Iran. A comparison made on gG gene in Iran with other countries show 0.3 to 14.3% variability in this gene. The greatest sequence similarity exists between sequences of gG in Iran and Sweden (EU018098 and EU018128) with a sequence similarity of 99.7% and the least relationship exists between sequences of gG gene of HSV-2 in Iran and USA (DQ236139) with a similarity of 85.7%. Key words : Herpes simplex virus type-2, gG gene, phylogenetic relationship, Iran.

Lactoferricin but not lactoferrin inhibit herpes simplex virus type 2 infection in mice

We have evaluated the potential of bovine lactoferrin and lactoferricin for their ability to prevent and/or treat genital HSV-2 infection in mice. We confirm previous data showing that both lactoferrin and lactoferricin have antiviral properties in vitro and can inhibit HSV-2 infection of GMK cells in a dose-dependent manner. When tested in vivo, lactoferricin but not lactoferrin was also a potent inhibitor of HSV-2 infection. When admixed with virus prior to inoculation, lactoferricin inhibited disease development and significantly reduced the viral load in a genital model of HSV-2 infection in mice. Lactoferrin and lactoferricin were also tested for their ability to stimulate the production of chemokines. Neither of the compounds induced the production of CCL3, CCL5, CXCL1 or CXCL2 by mouse splenocytes in vitro. However, when tested in vivo, both lactoferrin and lactoferricin were able to induce local vaginal production of CCL5. Lactoferrin also induced CXCL2 production. The prophylactic and/or therapeutic effects of lactoferrin or lactoferricin were also tested. But none of the compounds were efficient in blocking HSV-2 infection when given 24h prior to HSV-2 infection. Lactoferricin however showed promising results as a therapeutic agent and delayed both disease onset by 3days as well as reducing the viral load almost 15-fold when given as a single dose 24h post-infection. These data show that lactoferricin can block genital herpes infection in mice, and perhaps also be used for post-infection treatment.

Fatal multiorgan failure associated with disseminated herpes simplex virus-1 infection: a case report.

Herpes simplex virus type 1 (HSV-1) infections cause typical dermal and mucosal lesions in children and adults. Also complications to the peripheral and central nervous system, pneumonia or hepatitis are well known. However, dissemination to viscera in adults is rare and predominantly observed in immunocompromised patients. Here we describe the case of a 70-year-old male admitted with macrohematuria and signs of acute infection and finally deceasing in a septic shock with multi organ failure 17 days after admission to intensive care unit. No bacterial or fungal infection could be detected during his stay, but only two days before death the patient showed signs of rectal, orolabial and genital herpes infection. The presence of HSV-1 was detected in swabs taken from the lesions, oropharyngeal fluid as well as in plasma. Post-mortem polymerase chain reaction analyses confirmed a disseminated infection with HSV-1 involving various organs and tissues but excluding the central nervous system. Autopsy revealed a predominantly retroperitoneal diffuse large B-cell lymphoma as the suspected origin of immunosuppression underlying herpes simplex dissemination.

Emergence of Herpes Simplex Virus-1 Syncytial Variants With Altered Virulence for Mice After Selection With a Natural Carrageenan

Antiviral therapy against herpes simplex virus based on sulfated polysaccharides, like carrageenans, represents a new alternative for genital herpes infections treatment and arises the concern about the appearance of resistant viral populations. We characterized the F strain of herpes simplex virus-1 passaged in the presence of a natural carrageenan isolated from the red seaweed Gigartina skottbergii in view of the virulence for mice of isolated viral clones. Viral clones (syn14-1 and syn17-2) showed a syncytial phenotype and a mild resistance to carrageenan, heparin, acyclovir, and brivudine. Both clones were avirulent for BALB/c mice when inoculated intravaginally, whereas F strain produced high mortality. Attenuation correlated with low levels of TNF-[alpha], interleukin-6, and IFN-[gamma] in vaginal lavages although virus titers were similar to those obtained for F strain. On the contrary, they showed a marked virulence when inoculated intranasally leading to a generalized spreading of virus. Results confirm the hypothesis that selection of herpes simplex virus-1 with a carrageenan in vitro leads to the emergence of variants with a differential virulence when compared to the original virus. This finding should be addressed when an antiviral therapy against genital herpes infection employing a natural carrageenan is under consideration.

Pregnancy Outcome in Female Liver Transplant Recipients

Transplantation has become an available and successful treatment option for numerous congenital and acquired hepatic disorders. Studies have shown that when the prepregnancy recipient graft function is stable and adequate, pregnancy is normally well tolerated with favorable neonatal outcomes. However, there are reports of increased incidences of hypertension and preeclampsia as well as lower birth weights and prematurity. Patients administered tacrolimus-based therapies seem to have lower incidences of these complications. Case Reports The 5 reported patients, aged 23–37 years at the time of conception, were 2–11 years posttransplantation. A preterm delivery for fetal distress was the most clinically important complication among these patients. One episode of acute genital herpes infection, 1 liver hematoma in a patient who was anticoagulated owing to a history of deep vein thrombosis, and 1 case of wound infection postpartum were also observed. Despite these complications, all 5 pregnancies were successful. The mean gestational age at delivery was 35.2 weeks. No structural malformations or early complications were observed in the neonates. All cases showed stable liver parameters.

Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig

Genital herpes simplex virus (HSV) infections are common but results from vaccine trials with HSV-2 glycoprotein D (gD) have been disappointing. We therefore compared a similar HSV gD2 vaccine, to a further truncated gD2 vaccine, to a vaccine with gD2 plus gB2 and gH2/gL2 and to a vaccine with only gB2 and gH2/gL2 in a guinea pig model of genital herpes. All vaccines were administered with cationic liposome-DNA complexes (CLDC) as an adjuvant. All vaccines significantly decreased the severity of acute genital disease and vaginal virus replication compared to the placebo group. The majority of animals in all groups developed at least one episode of recurrent disease but the frequency of recurrent disease was significantly reduced by each vaccine compared to placebo. No vaccine was significantly more protective than gD2 alone for any of the parameters described above. No vaccine decreased recurrent virus shedding. When protection against acute infection of dorsal root ganglia and the spinal cord was evaluated all vaccines decreased the per cent of animal with detectable virus and the quantity of virus but again no vaccine was significantly more protective than another. Improvements in HSV-2 vaccines may require inclusion of more T cell targets, more potent adjuvants or live virus vaccines.

Genital herpes and HIV infection: Can we still exploit the intimate relationship?

South Africa is suffering the most severe HIV epidemic on earth. Prior to emergence of HIV/AIDS, conventional sexually transmitted infections (STIs) were endemic in many underprivileged communities as a result of many social factors. Since conventional STIs may act as co-factors in both acquisition and transmission of HIV, it was initially thought that improved treatment of these infections would result in a reduction of HIV transmission. As the HIV epidemic matured, the aetiological agents causing genital ulcer disease changed, with genital herpes emerging as the most potent STI co-factor in HIV spread. Despite learning more about herpes simplex virus/HIV interactions, attempts to utilise this knowledge to design HIV prevention strategies proved disappointing. However, the lessons learned may prove to be valuable in the future.

Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results: HSV-1 accounted for 78% of female and 85% of male genital herpes (GH) infections, and oral herpes (OH) infections presented as an acute febrile illness (AFI) in 51% of those 18 to 24 years old. HSV-2 accounted for 68% of GH infections among adults 25 or older. Conclusions: As seroprevalence for both HSV-1 and HSV-2 in the United States is decreasing, a growing college age cohort is at risk for primary HSV-1 infection. The proportion of GH caused by HSV-1 also continues to increase. This understanding has implications for clinical care, sexual health programming, and counseling strategies.

Still a long wait for approved HIV-protective gel

June 2013 – that’s the ‘realistic’ date by which vulnerable South African women can expect to begin using an officially approved vaginal microbicide gel that would provide them with an unprecedented tool to protect themselves from HIV infection. This is the belief of biochemist and epidemiologist, Dr Quarraisha Abdool Karim, who, together with her clinician and fellow epidemiologist husband, Professor Salim Abdool Karim, led the now world-renowned ‘proof of concept’ trial of tenofovir vaginal gel to prevent HIV infection in women. In a 3-year study of 889 women in both rural and urban KwaZulu-Natal, they demonstrated a 39% reduction in HIV infection and a 51% reduction in genital herpes infection among women who used the gel (containing 1% of the antiretroviral (ARV), tenofovir). The trial results dominated the XVIIIth International AIDS Conference in Vienna, Austria, in July and led to a clamour for confirmatory studies and fast-tracking of the gel, of which the efficacy increases with use. (Women who used the gel in more than 80% of their sex acts had a 54% reduction in HIV infections.) Unlike other HIV prophylactic trials that use available tablets, the tenofovir gel was manufactured only for the trial, run by the Durban-based Centre for AIDS Programme Research in South Africa (CAPRISA), of which the research couple are directors.