GSBS Student Publications

Title

A novel nuclear export activity in HIV-1 matrix protein required for viral replication

Student Author(s)

Stefan A. Dupont

Publication Date

1999-12-22

UMMS Affiliation

Program in Molecular Medicine

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences

Abstract

An important aspect of the pathophysiology of human immunodeficiency virus type-1 (HIV-1) infection is the ability of the virus to replicate in non-dividing cells. HIV-1 matrix (MA), the amino-terminal domain of the Pr55 gag polyprotein (Pr55), bears a nuclear localization signal that promotes localization of the viral preintegration complex to the nucleus of non-dividing cells following virus entry. However, late during infection, MA, as part of Pr55, directs unspliced viral RNA to the plasma membrane, the site of virus assembly. How MA can mediate these two opposing targeting functions is not understood. Here we demonstrate that MA has a previously undescribed nuclear export activity. Although MA lacks the canonical leucine-rich nuclear export signal, nuclear export is mediated through the conserved Crm1p pathway and functions in both mammalian cells and yeast. A mutation that disrupts the MA nuclear export signal (MA-M4) mislocalizes Pr55 and genomic viral RNA to the nucleus, thereby severely impairing viral replication. Furthermore, we show that MA-M4 can act in a dominant-negative fashion to mislocalize genomic viral RNA even in the presence of wild-type MA. We conclude that the MA nuclear export signal is required to counteract the MA nuclear localization signal, thus ensuring the cytoplasmic availability of the components required for virion assembly.

DOI of Published Version

10.1038/45272

Source

Nature. 1999 Dec 9;402(6762):681-5. Link to article on publisher's site

Journal/Book/Conference Title

Nature

Related Resources

Link to article in PubMed

PubMed ID

10604476

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