RESUMEN
The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2.
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Modelos Animales de Enfermedad , Herpes Genital , Herpesvirus Humano 2 , Seroconversión , Esparcimiento de Virus , Animales , Herpes Genital/inmunología , Herpes Genital/virología , Femenino , Herpesvirus Humano 2/inmunología , Esparcimiento de Virus/inmunología , Anticuerpos Antivirales/inmunología , Vagina/virología , Vagina/inmunología , Vagina/patología , Macaca mulattaRESUMEN
Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 µM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies.
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Herpesvirus Humano 2 , Arginina Deiminasa Proteína-Tipo 3 , Humanos , Herpesvirus Humano 2/fisiología , Herpesvirus Humano 2/genética , Arginina Deiminasa Proteína-Tipo 3/metabolismo , Citrulinación , Herpes Simple/virología , Herpes Simple/metabolismo , Replicación Viral/efectos de los fármacos , Animales , Herpes Genital/metabolismo , Herpes Genital/virología , Herpes Genital/tratamiento farmacológico , Arginina Deiminasa Proteína-Tipo 2/metabolismo , Antivirales/farmacologíaRESUMEN
BACKGROUND: Cervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions. CASE PRESENTATION: A 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae. There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms. CONCLUSION: Herpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment.
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Herpes Genital , Herpesvirus Humano 2 , Cervicitis Uterina , Humanos , Femenino , Adulto , Herpes Genital/diagnóstico , Herpes Genital/tratamiento farmacológico , Herpesvirus Humano 2/aislamiento & purificación , Cervicitis Uterina/virología , Cervicitis Uterina/tratamiento farmacológico , Cervicitis Uterina/diagnóstico , Cervicitis Uterina/microbiología , Imagen por Resonancia Magnética , Antibacterianos/uso terapéutico , Reacción en Cadena de la PolimerasaAsunto(s)
Antivirales , Herpes Genital , Herpes Zóster , Herpesvirus Humano 3 , Humanos , Masculino , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Herpes Genital/diagnóstico , Herpes Genital/tratamiento farmacológico , Herpes Genital/patología , Herpes Genital/virología , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/patología , Herpes Zóster/virología , Herpesvirus Humano 3/aislamiento & purificación , Anciano , Escroto/patología , Escroto/virología , Pene/patología , Pene/virologíaRESUMEN
The skin at the site of HSV-2 reactivation is enriched for HSV-2-specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells, we studied skin biopsies and HSV-2-reactive CD4+ T cells from PBMCs by T cell receptor (TCR) ß chain (TRB) sequencing before and after vaccination with a replication-incompetent whole-virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ TRB sequences from PBMCs in the skin TRB repertoire increased after the first vaccine dose. We found sustained expansion after vaccination of unique, skin-based T cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. In one participant, a switch in immunodominance occurred with the emergence of a TCR αß pair after vaccination that was not detected in blood. This TCRαß was shown to be HSV-2 reactive by expression of a synthetic TCR in a Jurkat-based NR4A1 reporter system. The skin in areas of HSV-2 reactivation possessed an oligoclonal TRB repertoire that was distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.
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Linfocitos T CD4-Positivos , Herpes Genital , Herpesvirus Humano 2 , Piel , Humanos , Herpesvirus Humano 2/inmunología , Piel/inmunología , Piel/virología , Herpes Genital/inmunología , Herpes Genital/prevención & control , Herpes Genital/virología , Linfocitos T CD4-Positivos/inmunología , Femenino , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Masculino , Adulto , Vacunación , Persona de Mediana EdadRESUMEN
This JAMA Insights examines the history, diagnosis, prevention, and stigma of genital herpes infection in the US and explores treatments such as suppressive therapy.
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Herpes Genital , Femenino , Humanos , Masculino , Antivirales/uso terapéutico , Herpes Genital/diagnóstico , Herpes Genital/tratamiento farmacológico , Herpes Genital/psicología , Herpes Genital/virología , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Estigma SocialRESUMEN
Background: The rising prevalence of herpes simplex type 2 (HSV-2) infection poses a growing global public health challenge. A comprehensive understanding of its epidemiology and burden disparities in China is crucial for informing targeted and effective intervention strategies in the future. Methods: We followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 31st, 2024. We synthesized HSV-2 seroprevalence data across different population types. We used random-effects models for meta-analyses and conducted meta-regression to assess the association between population characteristics and seroprevalence. Results: Overall, 23,999 articles were identified, and 402 publications (1,203,362 participants) that reported the overall seroprevalence rates (858 stratified measures) were included. Pooled HSV-2 seroprevalence among the general population (lower risk) was 7.7% (95% CI: 6.8-8.7%). Compared to the general population, there is a higher risk of HSV-2 prevalence among intermediate-risk populations (14.8%, 95% CI: 11.0-19.1%), and key populations (31.7%, 95% CI: 27.4-36.1%). Female sexual workers (FSWs) have the highest HSV-2 risk (ARR:1.69, 95% CI: 1.61-1.78). We found northeastern regions had a higher HSV-2 seroprevalence than other regions (17.0%, 95% CI: 4.3-35.6%, ARR: 1.38, 95% CI: 1.26-1.50, Northern China as the reference group). This highlighted the disparity by population risk levels and regions. We also found lower HSV-2 prevalence estimates in publications in Chinese bibliographic databases than those in English databases among key populations (such as MSM and HIV-discordant populations). Conclusion: There is a gradient increase in HSV-2 prevalence risk stratification. We also identified region, population, and age disparities and heterogeneities by publication language in the HSV-2 burden. This study provides guidance for future HSV-2 prevention to eliminate disparities of HSV-2 infection and reduce overall HSV-2 burden. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=408108, identifier CRD42023408108.
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Herpes Genital , Herpesvirus Humano 2 , Humanos , Herpesvirus Humano 2/inmunología , China/epidemiología , Herpes Genital/epidemiología , Estudios Seroepidemiológicos , Prevalencia , Femenino , Masculino , Factores de RiesgoAsunto(s)
Herpes Genital , Humanos , Herpes Genital/epidemiología , Femenino , Masculino , Antivirales/uso terapéuticoRESUMEN
This case report describes a pregnant patient with recent diagnosis of Human Immuno-Deficiency Virus (HIV) infection initiated on Anti-Retroviral Therapy (ART) in the second trimester, as well as high dose acyclovir high for large infected genital warts. She had no other HIV related opportunistic infections, and no prior anti tuberculosis treatment or preventive medication. Despite little response to acyclovir, patient was continuing on acyclovir for over 4 months. She subsequently developed recurrent anemia requiring frequent transfusion (14 units in total) over a 6-week period. On stopping acyclovir, the anemia subsided, a few weeks later she had a normal delivery, followed by surgical removal of the warts. At a follow-up 8 months later, she was well, with a healthy baby, and reported no other episodes of blood transfusion.
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Aciclovir , Anemia , Antivirales , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Recurrencia , Humanos , Femenino , Embarazo , Aciclovir/uso terapéutico , Aciclovir/efectos adversos , Aciclovir/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Adulto , Uganda , Resultado del Tratamiento , Herpes Genital/tratamiento farmacológico , Transfusión SanguíneaRESUMEN
INTRODUCTION: Low-income and middle-income countries (LMICs) have a high burden of herpes simplex virus type 2 (HSV-2) infection, which has been strongly associated with HIV. In 2001, the WHO hosted a workshop to set research priorities for HSV-2 in LMICs. Periodic re-evaluation of research priorities is essential to ensure effective allocation of resources. This study describes the progress made between 2000 and 2020 in addressing the priorities identified in two of the five thematic areas that were the workshop's focus: HSV-2 epidemiology and diagnostics. The remaining areas are addressed in a companion paper. METHODS: A systematic search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary and secondary research studies conducted in LMICs, written in English and published from 2000-2020 were included. Two independent researchers screened, identified papers and extracted preidentified variables from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS V.26. RESULTS: Overall, 4445 discrete papers were identified, of which 165 publications were eligible for inclusion. The highest general population HSV-2 prevalence was reported in South and West Africa. Prevalence was higher among women than men and increased with age. HSV-2 prevalence studies among key populations were few, and the majority were in East and South Asia. Cohort studies of HSV-2 incidence among younger populations (mean age=25 years) and HSV-2 infection prevalence in North Africa and the Middle East were few. The most researched topic in HSV-2 diagnostics addressed serological techniques and direct molecular biology. Studies of point-of-care testing were also few. CONCLUSION: HSV-2 research identified in LMICs has mainly addressed the epidemiology and diagnostics priorities identified by the 2001 WHO workshop. Unaddressed priorities include point-of-care testing, antiviral resistance and exploration of HSV-2 epidemiology in neglected geographical settings and population subgroups.
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Países en Desarrollo , Herpes Genital , Herpesvirus Humano 2 , Femenino , Humanos , Masculino , Herpes Genital/epidemiología , Herpes Genital/diagnóstico , Herpes Simple/epidemiología , Herpes Simple/diagnóstico , Herpesvirus Humano 2/aislamiento & purificación , Prevalencia , Organización Mundial de la SaludRESUMEN
INTRODUCTION: Reviewing and updating research priorities is essential to assess progress and to ensure optimal allocation of financial and human resources in research. In 2001, WHO held a research priority setting workshop for herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries (LMICs). This study aimed to describe progress between 2000 and 2020 in three of the five key research priority areas outlined in the workshop: HSV-2/HIV interactions, HSV-2 control measures and HSV-2 mathematical modelling. The remaining priorities are addressed in a companion paper. METHOD: A systematic literature search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary research studies based in LMICs, written in English and published on 2000-2020 were included. Papers were screened by two independent reviewers, and suitable variables were selected for manual extraction from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS. RESULTS: In total, 3214 discrete papers were identified, of which 180 were eligible for inclusion (HSV-2/HIV interactions, 98; control measures, 58; mathematical modelling, 24). Most studies were conducted in East Africa. The majority of the 2001 WHO HSV-2 research priorities were addressed at least in part. Overall, despite several studies describing a strong relationship between HSV-2 and the acquisition and transmission of HIV, HSV-2 control repeatedly demonstrated little effect on HIV shedding or transmission. Further, although mathematical modelling predicted that vaccines could significantly impact HSV-2 indicators, HSV-2 vaccine studies were few. Studies of antiviral resistance were also few. CONCLUSION: Since 2000, LMIC HSV-2 research addressing its control, HIV interactions and mathematical modelling has largely addressed the priorities set in the 2001 WHO HSV-2 workshop. However, key knowledge gaps remain in vaccine research, antiviral cost-effectiveness, antiviral resistance and specific geographical areas.
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Países en Desarrollo , Infecciones por VIH , Herpes Genital , Herpesvirus Humano 2 , Modelos Teóricos , Humanos , Investigación Biomédica/historia , Herpes Genital/prevención & control , Infecciones por VIH/prevención & control , Organización Mundial de la SaludRESUMEN
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are chronic, highly prevalent viral infections that cause significant morbidity around the world. HSV-2 is sexually transmitted and is the leading cause of genital ulcer disease (GUD). It also increases the risk of HIV acquisition, fueling the HIV epidemic. HSV-1 is typically acquired in childhood through nonsexual contact and contributes to oral and ocular disease, but it can also be sexually transmitted to cause GUD. Both HSV-1 and HSV-2 cause neonatal herpes and neurologic disease. Given the ubiquitous nature of HSV-1 and HSV-2 infections and the limited existing prevention and control measures, vaccination would be the most efficient strategy to reduce the global burden of morbidity related to HSV infection. Vaccine strategies include prophylactic vaccination, which would prevent infection among susceptible persons and would likely be given to adolescents, and therapeutic vaccinations, which would be given to people with symptomatic genital HSV-2 infection. This document discusses the vaccine value profile of both types of vaccines. This 'Vaccine Value Profile' (VVP) for HSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the HSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.
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Herpes Genital , Vacunas contra el Virus del Herpes Simple , Herpes Simple , Herpesvirus Humano 2 , Humanos , Herpesvirus Humano 2/inmunología , Vacunas contra el Virus del Herpes Simple/inmunología , Vacunas contra el Virus del Herpes Simple/administración & dosificación , Herpes Genital/prevención & control , Herpes Genital/inmunología , Herpes Simple/prevención & control , Herpes Simple/inmunología , Herpesvirus Humano 1/inmunología , VacunaciónRESUMEN
From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (TRM) CD8+ T cells that accumulate and persist in the genital skin at the local site of recrudescence are the "first responders" to viral reactivation, performing immunosurveillance and containment and aborting the ability of the virus to induce clinical lesions. This review describes the unique spatiotemporal characteristics, transcriptional signatures, and noncatalytic effector functions of TRM CD8+ T cells in the tissue context of human HSV-2 infection. We highlight recent insights into the intricate overlaps between intrinsic resistance, innate defense, and adaptive immunity in the tissue microenvironment and discuss how rapid virus-host dynamics at the skin and mucosal level influence clinical outcomes of genital herpes diseases.
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Linfocitos T CD8-positivos , Herpes Genital , Herpesvirus Humano 2 , Activación Viral , Latencia del Virus , Humanos , Herpes Genital/inmunología , Herpes Genital/virología , Activación Viral/inmunología , Herpesvirus Humano 2/inmunología , Herpesvirus Humano 2/fisiología , Linfocitos T CD8-positivos/inmunología , Latencia del Virus/inmunología , Memoria Inmunológica , Inmunidad Adaptativa , Piel/inmunología , Piel/virología , Inmunidad Innata , AnimalesRESUMEN
This report summarizes incidence rates and trends of sexually transmitted infections (STIs) from 2015 through 2023 among active component service members of the U.S. Armed Forces. The data compiled for this report are derived from the medical surveillance of chlamydia, gonorrhea, and syphilis as nationally notifiable diseases. Case data for 2 additional STIs, human papilloma virus (HPV) and genital herpes simplex virus (HSV), are also presented. The crude total case rates of chlamydia and gonorrhea initially rose by an average of 6.7% and 9.8% per year, respectively, until 2019. From 2020 onwards, rates steadily declined. By 2023, chlamydia rates had dropped by approximately 39%, while gonorrhea rates had fallen by more than 40% for female, and 19% for male, service members. Initially syphilis increased, on average, 10% annually from 2015 to 2019, then declined in 2020, but resumed its upward trend through 2023, nearly doubling the 2015 rate in 2023. The total crude annual incidence rates of genital HPV and HSV exhibited downward trends in general over the surveillance period, decreasing by 30.7% and 24.7%, respectively. Age- and gender-adjusted case rates for chlamydia, gonorrhea, and syphilis remain elevated within the U.S. Armed Forces compared to the general U.S. population, which may be due to factors that include mandatory STI screening, more complete reporting, incomplete adjustment for age distribution, and inequitable comparisons between the military active duty and general U.S. populations. Social restrictions enacted during the COVID-19 pandemic may have contributed to declines in true case rates and screening coverage.
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Infecciones por Chlamydia , Gonorrea , Herpes Genital , Personal Militar , Vigilancia de la Población , Enfermedades de Transmisión Sexual , Sífilis , Humanos , Estados Unidos/epidemiología , Personal Militar/estadística & datos numéricos , Femenino , Masculino , Adulto , Incidencia , Gonorrea/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Sífilis/epidemiología , Infecciones por Chlamydia/epidemiología , Adulto Joven , Herpes Genital/epidemiología , Infecciones por Papillomavirus/epidemiología , COVID-19/epidemiología , Persona de Mediana EdadRESUMEN
BACKGROUND: The current prevalence of Herpes simplex virus type 2 (HSV-2) infection is notably high, with individuals afflicted by HSV-2 facing recurrent outbreaks, challenges in achieving remission, and an elevated risk of HIV infection. This study aims to investigate the relationship between alcohol consumption and HSV-2 infection. METHODS: The data for this study were sourced from 7257 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. The target population consisted of adults with reliable HSV-2 plasma results, and alcohol consumption was assessed using self-report methods. We evaluated the odds ratio (OR) and 95% confidence interval (CI) for the association between alcohol consumption and HSV-2 infection. These estimations were derived from a logistic regression model that was adjusted for key confounding factors. Subgroup analysis specifically focused on alcohol consumption, and the interaction between HSV-2 infection, alcohol consumption, and other variables was assessed through stratified analysis. RESULTS: Among the 7,257 participants included, 89.8% (6,518/7,257) reported varying levels of alcohol consumption history. Compared to individuals who never drinkers, the adjusted odds ratios (ORs) for former drinkers, light drinkers, moderate drinkers, and heavy drinkers were 1.79 (95% CI: 1.34-2.4, p < 0.001), 1.38 (95% CI: 1.07-1.77, p = 0.012), 1.49 (95% CI: 1.15-1.94, p = 0.003), and 1.47 (95% CI: 1.14-1.9, p = 0.003), respectively. The results remained stable in subgroup analyses and sensitivity analyses. CONCLUSION: Current research indicates that individuals with a history of alcohol consumption exhibit a higher risk of HSV-2 infection compared to those who have never drinkers.
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Consumo de Bebidas Alcohólicas , Herpes Genital , Herpesvirus Humano 2 , Encuestas Nutricionales , Humanos , Masculino , Femenino , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Adulto , Estudios Transversales , Persona de Mediana Edad , Herpes Genital/epidemiología , Adulto Joven , Prevalencia , Oportunidad Relativa , Factores de Riesgo , Herpes Simple/epidemiología , AncianoRESUMEN
Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.
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Antivirales , Modelos Animales de Enfermedad , Herpes Genital , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Queratitis Herpética , Animales , Conejos , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Herpes Genital/tratamiento farmacológico , Herpes Genital/virología , Queratitis Herpética/tratamiento farmacológico , Queratitis Herpética/virología , Chlorocebus aethiops , Femenino , Células Vero , Interferón alfa-2/administración & dosificación , Interferón alfa-2/uso terapéutico , Replicación Viral/efectos de los fármacos , Administración Tópica , Soluciones Oftálmicas , Interferón-alfa/administración & dosificación , HumanosRESUMEN
BACKGROUND: Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus. Contemporary US population-based epidemiologic data on genital herpes are limited. This study aimed to provide nationally representative estimates of genital herpes prevalence and treatment using a large US health insurance claims database. METHODS: This observational cohort study used administrative claims data from HealthVerity. Crude and age- and sex-standardized prevalence rates of genital herpes and recurrent genital herpes were calculated for the years 2019 to 2021. The distribution of patients with prevalent genital herpes who received episodic or suppressive antiviral therapy was also estimated. RESULTS: From 2019 to 2021, the standardized prevalence of genital herpes and recurrent genital herpes ranged from 236 to 280 cases per 100,000 person-years and 81 to 98 cases per 100,000 person-years, respectively. The prevalence of genital herpes was highest among those aged 25 to 29 years (prevalence range, 497-582 years), female patients (prevalence range, 348-404 years), and those with a history of HIV infection (prevalence range, 1608-2080 years). The prevalence of recurrent genital herpes was also highest in these groups. From 2019 to 2021, two-thirds of patients (65%-68%) with prevalent genital herpes received antiviral medications; the majority received episodic therapy (80%) rather than suppressive therapy (20%). CONCLUSIONS: The burden of genital herpes and recurrent genital herpes in the United States is substantial, with the highest rates observed in young adults, women, and immunocompromised individuals. About two-thirds receive antiviral treatment each year.
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Antivirales , Herpes Genital , Humanos , Herpes Genital/epidemiología , Herpes Genital/tratamiento farmacológico , Femenino , Antivirales/uso terapéutico , Masculino , Adulto , Prevalencia , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto Joven , Adolescente , Anciano , Estudios de Cohortes , Recurrencia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , NiñoRESUMEN
Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease.