Molecular biology of trichomonasviruses

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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.