A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions

Author:

Gupta, K.

Ott, D.

Hope, T. J.

Siliciano, R. F.

Boeke, J. D.
Author Address

Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, Frederick, MD 21702 USA. Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. Boeke JD Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.

Abstract:

Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIG) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55(Gag) and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4(+) T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55(Gag) and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport.

See More

Author Address