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.

家族的几种dsRNA病毒partitiviridae和totiviridae持续感染了寄生原生动物，包括 来自隐孢子虫（肠道疾病），贾第氏病（肠道疾病）的重要人类病原体， 利什曼原虫（皮肤，粘膜和内脏形式的疾病）和毛毛虫（泌尿生殖器 疾病）。利什曼尼亚和毛毛虫的最新研究提供了证据表明他们的各自 Totiviruses，Leishmania RNA病毒和阴道病毒（TVV），有助于原生动物 通过诱导人类细胞促炎反应的相关疾病，这会影响程度和 周围组织中炎症的性质。这样的结果导致了一个普遍的假设，即广泛的假设 寄生虫原生动物的普遍DSRNA病毒通常会影响原生动物与人类细胞的相互作用 对加剧各自的人类疾病或其他方式产生重要后果的方式 增强这些原生动物在自然生命周期中的生存或传播。一个广泛的目标 这个新兴领域是更好地了解原生动物病毒对原生动物和原生动物的影响 人类细胞。当前的提案集中于TVVS（Trichomonasviruess）及其宿主T.阴道菌（T. Vaginalis） 引起全球最常见的非病毒性传播疾病，也与 增加艾滋病毒的获取和传播，早产和低出生体重。 T.阴道是 现在被公认为是与人类健康的主要相关性较高的病原体之一，尤其是 妇女和婴儿的健康，在美国和世界各地，尤其是在非裔美国人和低点 收入经济体。这里提出的研究将增强对TVV分子生物学的理解 并将开发工具，试剂和靶标，以进一步研究这些病毒作为致病性决定因素 对于毛肌瘤及其相关的问题。该提议的具体目的是：目标1，进步 TVV病毒体的结构研究；目标2，以表征依赖一个或多个的DSRNA卫星 用于复制和维护的TVV物种；和目标3，以剖析RNA包装，合成和 TVV基因组中的翻译。