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MX2 Viral Substrate Breadth and Inhibitory Activity Are Regulated by Protein Phosphorylation

ABSTRACT: Productive infection by human immunodeficiency virus type-1 (HIV-1) requires the import of viral replication complexes into the nuclei of infected cells. Myxovirus resistance 2 (MX2/MxB) blocks this step, halting nuclear accumulation of viral DNA and virus replication. Here, we identify positions in MX2 whose phosphorylation status reduces or enhances antiviral function (hypomorphic and hypermorphic variants, respectively). Importantly, hypermorphic mutant proteins not only increased inhibitory activity against wild-type HIV-1 but can also exhibit antiviral capabilities against HIV-1 capsid mutant viruses that are resistant to wild-type MX2. Furthermore, some of these proteins were also able to inhibit retroviruses that are insensi- tive to MX2. Therefore, we propose that phosphorylation comprises a major element of MX2 regulation and substrate determination.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Glioblast, Astrocyte

SUBMITTER: Steven Lynham

LAB HEAD: Professor Michael Malim

PROVIDER: PXD035305 | Pride | 2022-07-21

REPOSITORIES: Pride

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