Inhibition of Herpes Simplex Virus Type 2 by Tenofovir

替诺福韦对 2 型单纯疱疹病毒的抑制作用

• 批准号: 8492027
• 负责人: Nicholas J Van Wagoner
• 金额: $ 13.36万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-18 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492027
• 关键词: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Retroviral Agents; Antibodies; Antiviral Agents; Archives; Basic Science; Biological Assay; Cells; Chronic; Cidofovir; Clinical; Clinical Research; Clinical Services; Cohort Analysis; Data; Diagnosis; Disease; Disease Progression; Drug resistance; Excipients; Exhibits; Famciclovir; Foscarnet; Frequencies; Funding; Future; General Population; Genome; Grant; HIV; HIV therapy; HIV-1; Human; Human Herpesvirus 2; Immunocompromised Host; In Vitro; Incidence; Infection; K-Series Research Career Programs; Life; Light; Measures; Methodology; Morbidity - disease rate; Natural History; New Agents; Participant; Patient Care; Patients; Penetration; Persons; Pharmaceutical Preparations; Phase; Population; Prevention; Randomized Controlled Trials; Recurrence; Regimen; Research; Research Design; Role; Sampling; Scientist; Serologic tests; Seroprevalences; Serum; Severities; Simplexvirus; Techniques; Tenofovir; Tenofovir disoproxil fumarate; Testing; Therapeutic Agents; Time; Training; Ulcer; Viral; Viral Drug Resistance; Virus Diseases; Virus Shedding; antiretroviral therapy; base; clinically relevant; clinically significant; design; improved; in vitro activity; in vivo; meetings; microbicide; nucleoside analog; prevent; public health relevance; skills; therapy resistant; transmission process; vaginal microbicide; valacyclovir; viral detection; viral resistance; virology

DESCRIPTION (provided by applicant): Herpes Simplex Virus Type 2 (HSV-2) is a common infection that causes a spectrum of clinical disease from mild mucocutaneous, anogenital ulcers to life-threatening conditions. Prevention of HSV-2 infection is difficult and current therapy for HSV-2 is not completely effective. Immunocompromised persons such as those with HIV are particularly vulnerable to HSV-2, manifesting more severe disease and developing higher rates of resistance to therapy. For these reasons, new, more effective therapeutic agents are needed to prevent and treat HSV-2 infection and disease, respectively, especially in persons with HIV. Recent clinical and in vitro data suggest that agents, developed for the treatment of HIV, may also have activity against HSV-2. Most compelling are data suggesting that a Tenofovir Disoproxil Fumarate (TDF)-based, vaginal microbicide reduces HSV-2 acquisition. As an extension of this finding and based on our preliminary research, I hypothesize that TDF will have direct activity against HSV-2 in vitro and that orally delivered TDF, as a component of HIV therapy, will have activity against HSV-2 in vivo. To test this hypothesis, I propose the following independent but inter-related aims. Aim 1: Investigate the potential inhibitory role of TDF on HSV-2 replication in vitro. Aim 2: Determine the potential suppressive effect of systemically delivered TDF on HSV-2 infection and its suppressive effect on subclinical HSV-2 viral shedding in vivo. Using bidirectional and translational techniques as outlined in this proposal, I will establish a fundamental understanding of TDF's action on HSV-2 while providing information about clinical relevance. Of equal importance, this career development award and the research aims as outlined above are designed to provide me with additional training in virology, clinical study design, methodology, and statistical analysis to meet my specific educational needs. The opportunities created by this career development award will culminate in the creation of a translational scientist with the skills necessary to adeptly, ethically, and accurately answer important scientific questions related to HSV-2 prevention and treatment. It will also help me to successfully obtain future independent funding, and most importantly, improve patient care.

描述（由申请方提供）：单纯疱疹病毒2型（HSV-2）是一种常见感染，可引起一系列临床疾病，从轻度皮肤粘膜、肛门生殖器溃疡到危及生命的疾病。HSV-2感染的预防是困难的，并且目前对HSV-2的治疗不是完全有效的。免疫功能低下的人，如艾滋病毒感染者，特别容易感染HSV-2，表现出更严重的疾病，并对治疗产生更高的耐药性。由于这些原因，需要新的、更有效的治疗剂来分别预防和治疗HSV-2感染和疾病，特别是在HIV感染者中。最近的临床和体外数据表明，开发用于治疗HIV的药物也可能具有抗HSV-2的活性。最令人信服的数据表明，替诺福韦二异丙酯富马酸盐（TDF）为基础的，阴道杀微生物剂减少HSV-2的收购。作为这一发现的延伸，并根据我们的初步研究，我假设TDF将有直接的活性，对HSV-2的体外和口服给药的TDF，作为艾滋病毒治疗的一部分，将有活性，对HSV-2的体内。为了检验这一假设，我提出了以下独立但相互关联的目标。目的1：研究TDF对HSV-2复制的抑制作用。目标二：确定全身递送的TDF对HSV-2感染的潜在抑制作用及其对体内亚临床HSV-2病毒脱落的抑制作用。使用双向和翻译技术概述了本建议，我将建立一个基本的了解TDF的行动对HSV-2，同时提供有关临床相关性的信息。同样重要的是，这个职业发展奖和上述研究目标旨在为我提供病毒学，临床研究设计，方法学和统计分析方面的额外培训，以满足我的特定教育需求。这个职业发展奖创造的机会将最终创造一个具有熟练，道德和准确回答与HSV-2预防和治疗相关的重要科学问题所需技能的翻译科学家。这也将帮助我成功地获得未来的独立资金，最重要的是，改善病人护理。