Map Reveals How Zika Virus Associates with Host Cell Proteins

Zika virus is a membrane enveloped Flavivirus with a positive strand RNA genome, transmitted by Aedes mosquitoes. The geographical range of ZIKV has dramatically expanded in recent decades resulting in increasing numbers of infected individuals, and the spike in ZIKV infections has been linked to significant increases in both Guillain-Barré syndrome and microcephaly. While a large number of host proteins have been physically and/or functionally linked to other Flaviviruses, very little is known about the virus-host protein interactions established by ZIKV.

Investigators at the University of Toronto (Canada) generated 10 strains of human cells with each strain expressing one Zika protein. By adding a low molecular weight "epitope" tag to each viral protein they could retrieve these proteins using an antibody that bound to the tag. In addition, they used proximity labeling to identify closely linked viral and human proteins.

Results reported in the July 23, 2018, online edition of the journal Molecular & Cellular Proteomics revealed a set of host cell protein interaction profiles for each of the ten polypeptides encoded in the ZIKV genome. This protein topology network comprised 3033 interactions amongst 1224 unique human polypeptides. This network was enriched in proteins with roles in polypeptide processing and quality control, vesicle trafficking, RNA processing, and lipid metabolism. More than 60% of the network components had been previously implicated in other types of viral infections; the remaining proteins comprised hundreds of new putative ZIKV functional partners.

"A better understanding of these processes will allow us to identify specific vulnerabilities in the virus life cycle where antiviral drugs can be targeted," said senior author Dr. Brian Raught, professor of proteomics and molecular medicine at the University of Toronto.

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