Molecular biology of trichomonasviruses

滴虫病毒的分子生物学

• 批准号: 9522102
• 负责人: MAX L. NIBERT
• 金额: $ 24.42万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9522102
• 关键词: Affect; African American; Amino Acid Sequence; Antisense RNA; Biology; Capsid Proteins; Cells; Chemistry; Collection; Cryptosporidium; Cryptosporidium parvum; Cutaneous; Data; Detection; Development; Disease; Disease model; Double Stranded RNA Virus; Double-Stranded RNA; Elements; Enteral; Extravasation; Family; Genetic; Genetic Transcription; Genitourinary system; Genome; Giardia; Giardia lamblia; HIV; Health; Helper Viruses; Human; IRF3 gene; Individual; Infant Health; Infection; Inflammation; Internal Ribosome Entry Site; Leishmania; Leishmaniavirus; Life Cycle Stages; Literature; Low Birth Weight Infant; Low income; Maintenance; Mammalian Cell; Maps; Mastigophora; Molecular Biology; Mucous Membrane; Mus; Nature; Partitiviridae; Pathogenicity; Pattern; Phenotype; Plasmids; Premature Birth; Prevalence; Proteins; Protozoa; PubMed; Publishing; RNA; RNA Viruses; Reagent; Reporter; Reporter Genes; Resolution; Resources; Ribosomal Frameshifting; Risk; Role; Satellite Viruses; Sexual Transmission; Sexually Transmitted Diseases; Signal Transduction; Site; Structure; System; TLR3 gene; Tissues; Totivirus; Transcript; Translations; Trichomonas; Trichomonas Infections; Trichomonas vaginalis; Urogenital Diseases; Viral Genome; Virion; Virus; Visceral; Woman; Work; aged; base; experimental study; human disease; image reconstruction; member; neglect; new technology; pathogen; predictive test; response; tool; transmission process

Several dsRNA viruses of families Partitiviridae and Totiviridae persistently infect parasitic protozoa, including important human pathogens from genera Cryptosporidium (enteric disease), Giardia (enteric disease), Leishmania (cutaneous, mucocutaneous, and visceral forms of disease), and Trichomonas (urogenital disease). Recent studies of Leishmania and Trichomonas have provided evidence that their respective totiviruses, Leishmania RNA virus and Trichomonas vaginalis virus (TVV), contribute to the protozoan- associated diseases by inducing proinflammatory responses by human cells, which influence the degree and nature of inflammation in surrounding tissues. Such results have led to a general hypothesis that the widely prevalent dsRNA viruses of parasitic protozoa may commonly affect protozoan interactions with human cells in ways that have important consequences for exacerbating the respective human diseases or for otherwise enhancing the survival or transmission of these protozoa during their natural life cycles. A broad objective in this emerging field is to better understand the effects of protozoal dsRNA viruses on both protozoan and human cells. The current proposal is focused on TVVs (trichomonasviruses) and their host T. vaginalis, which causes the most common, nonviral sexually transmitted disease worldwide and is also associated with increased acquisition and transmission of HIV, as well as preterm delivery and low birth weight. T. vaginalis is now recognized as one of the more neglected pathogens of major relevance to human health, especially women's and infants' health, in the US and around the world, especially among African-Americans and in low- income economies. The studies proposed here will enhance understanding of the molecular biology of TVVs and will develop tools, reagents, and targets for further studies of these viruses as pathogenicity determinants for trichomoniasis and its associated problems. The specific aims of this proposal are: Aim 1, to advance structural studies of TVV virions; Aim 2, to characterize dsRNA satellites that depend on one or more of the TVV species for replication and maintenance; and Aim 3, to dissect signals for RNA packaging, synthesis, and translation in the TVV genome.

部分病毒科和全病毒科的几种dsRNA病毒持续感染寄生原生动物，包括 来自隐孢子虫属（肠道疾病），贾第虫属（肠道疾病）， 利什曼原虫（皮肤、粘膜皮肤和内脏形式的疾病）和毛滴虫（泌尿生殖道 疾病）。最近对利什曼原虫和毛滴虫的研究提供了证据，表明它们各自的 利什曼原虫RNA病毒和阴道毛滴虫病毒（TVV），有助于原生动物- 通过诱导人类细胞的促炎反应来治疗相关疾病， 周围组织炎症的性质。这样的结果导致了一个普遍的假设， 寄生原生动物的流行dsRNA病毒通常可以影响原生动物与人类细胞的相互作用， 对加重相应的人类疾病或其他疾病具有重要后果的方式 从而增强这些原生动物在其自然生命周期中的存活或传播。一个广泛的目标， 这一新兴领域是为了更好地了解原生动物dsRNA病毒对原生动物和 人体细胞目前的建议集中在TVV（毛滴虫病毒）和它们的宿主T。流浪汉， 导致世界范围内最常见的非病毒性性传播疾病， 艾滋病毒感染和传播增加，以及早产和出生体重不足。T.迷走神经 现在被认为是与人类健康有重大关系的更被忽视的病原体之一，特别是 妇女和婴儿的健康，在美国和世界各地，特别是在非洲裔美国人和低， 收入经济体。本文的研究将有助于加深对TVV分子生物学的理解 并将开发工具、试剂和靶标，用于进一步研究这些病毒作为致病性决定因素的作用 治疗滴虫病及其相关问题。本提案的具体目标是： TVV病毒粒子的结构研究;目的2，表征依赖于一个或多个 用于复制和维持的TVV物种;目标3，剖析RNA包装、合成和表达的信号 TVV基因组中的翻译。