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Mechanisms of RNA Virus Replication

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Examining Conserved Mechanisms of (+)RNA Virus Replication

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Project Description:

Emerging infectious diseases pose a serious threat to U.S. national security and the economy. In the ten years between 2000 and 2010, newly emerged infectious diseases caused $200 billion in economic losses and more than 2.7 million deaths. Viruses with RNA genomes, for example the Zika virus, compose one-third of all emerging infectious diseases [3]. Accordingly, there is an urgent need to understand conserved RNA virus replication strategies. Not meeting this need represents an important problem because, without correction, we are prone to wide-spread morbidity and mortality caused by a newly emerged virus. The long-term goal of the Kopek lab is to identify the common replication strategies of RNA viruses. Viruses with positive-strand RNA [(+)RNA)] genomes represent the majority of human, animal, and plant viral pathogens. One common replication feature of (+)RNA viruses is that they all replicate their RNA genome in association with host intracellular membranes. At these membranes, the (+)RNA viruses form virus replication complexes where they replicate their RNA genome. Recent work has shown the involvement of cellular lipid synthesis pathways and specific lipid requirements in viral genome replication for many (+)RNA viruses, in agreement with the fact that lipids are major components of membranes. Despite the considerable importance of membrane-associated genome replication, many questions remain, including the role of lipids in replication complex structure and formation and how viruses manipulate the lipid biosynthetic pathways. The proposed research is expected to clarify the role of specific lipids and identify how the (+)RNA virus, Flock House virus, manipulates cellular lipid synthesis pathways. This basic research is significant because it may have broader impacts on the development of viral control strategies.

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