Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA

Alice G. Bukrinskaya, Anuja Ghorpade, Nina K. Heinzinger, Thomas E. Smithgall, Robert E Lewis, Mario Stevenson

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

In the replication of human immunodeficiency virus type 1 (HIV-1), gag MA (matrix), a major structural protein of the virus, carries out opposing targeting functions. During virus assembly, gag MA is cotranslationally myristoylated, a modification required for membrane targeting of gag polyproteins. During virus infection, however, gag MA, by virtue of a nuclear targeting signal at its N terminus, facilitates the nuclear localization of viral DNA and establishment of the provirus. We now show that phosphorylation of gag MA on tyrosine and serine prior to and during virus infection facilitates its dissociation from the membrane, thus allowing it to translocate to the nucleus. Inhibition of gag MA phosphorylation either on tyrosine or on serine prevents gag MA-mediated nuclear targeting of viral nucleic acids and impairs virus infectivity. The requirement for gag MA phosphorylation in virus infection is underscored by our finding that a serine/threonine kinase is associated with virions of HIV-1. These results reveal a novel level of regulation of primate lentivirus infectivity.

Original languageEnglish (US)
Pages (from-to)367-371
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number1
DOIs
StatePublished - Jan 9 1996

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Viral DNA
Virus Diseases
HIV-1
Phosphorylation
Serine
Tyrosine
Primate Lentiviruses
Viral Structural Proteins
gag Gene Products
Nuclear Matrix
Virus Assembly
Proviruses
Membranes
Protein-Serine-Threonine Kinases
Virion
Nucleic Acids
Viruses

ASJC Scopus subject areas

  • General

Cite this

Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA. / Bukrinskaya, Alice G.; Ghorpade, Anuja; Heinzinger, Nina K.; Smithgall, Thomas E.; Lewis, Robert E; Stevenson, Mario.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 1, 09.01.1996, p. 367-371.

Research output: Contribution to journalArticle

Bukrinskaya, Alice G. ; Ghorpade, Anuja ; Heinzinger, Nina K. ; Smithgall, Thomas E. ; Lewis, Robert E ; Stevenson, Mario. / Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 1. pp. 367-371.
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