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BINDING OF ADENOVIRUS EARLY PROTEIN E411K TO RNA HELICASE DDX6

Abstract

Adenovirus is a non-enveloped, icosahedral DNA virus with a linear, double-stranded genome. Over 50 serotypes of human adenovirus have been identified and cause a variety of illnesses, including: conjunctivitis, gastroenteritis, and respiratory infections. Largely due to the efficacy with which adenovirus is able to infect host cells and replicate, it has been demonstrated to be an indispensable tool for a variety of therapeutic purposes including gene therapies, immunization delivery, and oncolytic therapies. Consequently, ongoing research largely focuses on adenovirus’ improvement as a vector and a deepening understanding of host responses to infection. The life cycle of adenovirus is divided into early and late phases, with early proteins being largely regulatory, and late proteins being of a structural nature. Previous research has indicated that among the many roles of early proteins, arguably some of the most vital exist solely to evade the numerous antiviral responses mounted by infected host cells and establish a favorable environment for viral replication. Such proteins have been demonstrated to re-localize key cellular proteins, most notably proteins found within mRNA processing bodies (p-bodies). Among the re-localized p-body proteins are the scaffolding protein, Pat1b, and RNA helicase, DDX6. Pat1b and DDX6 are known to work together to post-transcriptionally control the expression of genes. Additionally, research has indicated that the interaction between DDX6 and the 11-kDa protein E411K reliably enhances viral replication. Further research is needed to understand the nature of this interaction, and could provide valuable insight to the mechanisms through which adenovirus modulates antiviral responses. Specifically, our project aims to identify, via immunofluorescence, (1) the intracellular locations of wild-type Pat1b following adenovirus infection and (2) the location of Pat1b and DDX6 following infection with mutant adenovirus that fails to express E411K.

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