HIV-1-induced nuclear invaginations mediated by VAP-A, ORP3, and Rab7 complex explain infection of activated T cells.

ABSTRACT: The mechanism of human immunodeficiency virus 1 (HIV-1) nuclear entry, required for productive infection, is not fully understood. Here, we report that in HeLa cells and activated CD4⁺ T cells infected with HIV-1 pseudotyped with VSV-G and native Env protein, respectively, Rab7⁺ late endosomes containing endocytosed HIV-1 promote the formation of nuclear envelope invaginations (NEIs) by a molecular mechanism involving the VOR complex, composed of the outer nuclear membrane protein VAP-A, hyperphosphorylated ORP3 and Rab7. Silencing VAP-A or ORP3 and drug-mediated impairment of Rab7 binding to ORP3-VAP-A inhibited the nuclear transfer of the HIV-1 components and productive infection. In HIV-1-resistant quiescent CD4⁺ T cells, ORP3 was not hyperphosphorylated

SUBMITTER: Santos MF 

PROVIDER: S-EPMC10415338 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature