Phosphoinositide 3'-Kinase ? Facilitates Polyomavirus Infection.

ABSTRACT: Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3'-kinase ? (PI3K?) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV. PI3K? appears less important for polyomavirus infection than PI3K?. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3K? inhibited infection by authentic JCPyV and by JC pseudovirus. PI3K? knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3K? gene into the PI3K? knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3K? pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3K? facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3K? signaling may have a role in managing polyomavirus infections.

SUBMITTER: Clark P 

PROVIDER: S-EPMC7589550 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature