Flavivirus is a genus of viruses that includes west Nile virus and cause severe disease such as yellow fever. Flavivirus genomic RNA replication occurs on the rough endoplasmic reticulum, in membranous compartments, and the focus of Dr. Chao and his advisor Dr. Stephen Harrison’s research at Harvard was the fusion of the viral and cellular membranes. Cellular entry by the virus requires this membrane fusion and in order to do so, viral fusion proteins undergo dramatic conformational rearrangements. These proteins must undergo conformational changes to create a thermodynamically favorable chemical reaction and overcome the energetic barriers to merge the two membranes and create hemisfusion. They discovered that the envelope protein comprised of three main domains, with one being largely hydrophobic and involved in the fusion loop. In its pre-fusion state, the hydrophobic domain is tucked in the protein, however the hydrophobic domain extends into cell membrane then collapses to bring membrane together and create hemifusion and full pore opening.
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