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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：单纯疱疹病毒2型（HSV-2）是一种常见的感染，可引起各种临床疾病，这些临床疾病从轻度粘膜性，肛门生殖器性溃疡到危及生命的疾病。预防HSV-2感染很困难，HSV-2的当前治疗并不完全有效。诸如艾滋病毒的人（例如艾滋病毒）尤其容易受到HSV-2的影响，表现出更严重的疾病并产生更高的耐药率。由于这些原因，需要新的，更有效的治疗剂来预防和治疗HSV-2感染和疾病，尤其是在HIV患者中。最近的临床和体外数据表明，用于治疗HIV的药物也可能具有针对HSV-2的活性。最引人注目的数据表明，基于阴道杀菌剂的替诺福韦毒素（TDF）降低了HSV-2的采集。作为这一发现的扩展，并基于我们的初步研究，我假设TDF在体外对HSV-2具有直接的活性，并且作为HIV治疗的一部分，口服交付的TDF将具有针对HSV-2 IN VIVO的活性。为了检验这一假设，我提出了以下独立但相互关联的目的。目标1：研究TDF在体外HSV-2复制中的潜在抑制作用。目标2：确定系统递送的TDF对HSV-2感染的潜在抑制作用及其对亚临床HSV-2病毒脱落的抑制作用。使用本提案中概述的双向和翻译技术，我将在提供有关临床相关性的信息的同时，对TDF对HSV-2的行动建立基本理解。同样重要的是，这项职业发展奖和上述旨在的研究旨在为我提供有关病毒学，临床研究设计，方法论和统计分析的其他培训，以满足我的特定教育需求。该职业发展奖创建的机会将在创建一位翻译科学家的情况下达到顶峰，其技能是熟练，道德和准确地回答与HSV-2预防和治疗有关的重要科学问题。这也将帮助我成功获得未来的独立资金，最重要的是，改善患者护理。