Molecular biology of trichomonasviruses

Partitiviridae和Totiviridae的几种dsRNA病毒持续感染寄生原虫，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、粘膜皮肤和内脏疾病)和滴虫(泌尿生殖系统 疾病)。最近对利什曼原虫和滴虫的研究提供了证据，证明它们各自 利什曼原虫RNA病毒和阴道毛滴虫病毒(TVV)是原生动物的致病因子。 通过诱导人类细胞的促炎反应，影响疾病的程度和程度 周围组织的炎症性质。这样的结果导致了一个普遍的假设，即广泛的 寄生原虫流行的dsRNA病毒可能通常会影响原虫与人类细胞的相互作用 对加重各自的人类疾病或其他方面具有重要后果的方式 加强这些原生动物在其自然生命周期中的生存或传播。一个广泛的目标是 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 人类细胞。目前的建议集中在电视病毒(滴虫病毒)及其宿主阴道毛滴虫上，这 导致全世界最常见的非病毒性性传播疾病，也与 艾滋病毒的获取和传播增加，以及早产和低出生体重。阴道毛滴虫 现在被认为是对人类健康具有重大意义的更被忽视的病原体之一，特别是 在美国和世界各地，特别是在非裔美国人和低收入群体中，妇女和婴儿的健康 收入经济。本文提出的研究将增进对电视病毒分子生物学的理解。 并将为进一步研究这些病毒作为致病决定因素而开发工具、试剂和靶标 滴虫病及其相关问题。这项建议的具体目标是：目标1，推进 TVV病毒粒子的结构研究；目标2，表征依赖于一个或多个 TVV物种用于复制和维护；以及目标3，剖析RNA包装、合成和 TVV基因组中的翻译。

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.