Open AccessPhosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA.
Author(s) -
A. G. Bukrinskaya,
Anuja Ghorpade,
Nina K. Heinzinger,
Thomas E. Smithgall,
Robert E. Lewis,
Mario Stevenson
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.1.367
Subject(s) - biology , group specific antigen , virus , provirus , phosphorylation , virology , nuclear transport , nuclear localization sequence , myristoylation , serine , viral replication , infectivity , capsid , cell nucleus , microbiology and biotechnology , biochemistry , cytoplasm , gene , genome
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.