Ag. Bukrinskaya et al., PHOSPHORYLATION-DEPENDENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND NUCLEAR TARGETING OF VIRAL-DNA, Proceedings of the National Academy of Sciences of the United Statesof America, 93(1), 1996, pp. 367-371
In the replication of human immunodeficiency virus type 1 (HIV-1), gag
MA (matrix), a major structural protein of the virus, carries out opp
osing targeting functions. During virus assembly, gag MA is cotranslat
ionally myristoylated, a modification required for membrane targeting
of gag polyproteins. During virus infection, however, gag MA, by virtu
e of a nuclear targeting signal at its N terminus, facilitates the nuc
lear localization of viral DNA and establishment of the provirus, We n
ow show that phosphorylation of gag MA on tyrosine and serine prior to
and during virus infection facilitates its dissociation from the memb
rane, thus allowing it to translocate to the nucleus. Inhibition of ga
g MA phosphorylation either on tyrosine or on serine prevents gag MA-m
ediated nuclear targeting of viral nucleic acids and impairs virus inf
ectivity. The requirement for gag MA phosphorylation in; virus infecti
on is underscored by our finding that a serine/threonine kinase is ass
ociated with virions of HIV-1. These results reveal a novel level of r
egulation of primate lentivirus infectivity.