Identification of Host Factors for Rift Valley Fever Phlebovirus

A zoonotic pathogen Rift Valley Fever phlebovirus is well circulated among humans and livestock, characterized as causing abortion with almost 100% mortality rates in newborn animals. Presently, lack of FDA-approved antiviral drug/ license vaccine to control RFV in humans and detailed knowledge of viral protein function is necessary to successfully develop antiviral therapies. RVFV is susceptible to infect and replicate in a variety of cell types from frogs, pigs, elk, mule deer, reptiles. To analyze the host factor role, CRISPR-Cas9 knockout screening in A549 human cells and validated the function of the selected gene candidates by measuring the intracellular viral RNA accumulation, western blot, and RT-qPCR for two viruses, RVFV and La Crosse Encephalitis Virus (LACV). A gene knockout of member of WD repeat protein family (WDR7) in A549 human cell line is confirmed as important factor in the replication of two different viruses from Bunyavirales order. WDR7 gene disruption affects intracellular viral RNA accumulation primarily in the late phase of RVFV replication cycle and at the early phase of the LACV replication cycle. Moreover, the finding also highlight that WDR7 could be used as potential drug target for further antiviral development.
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