       Document 0609
 DOCN  M9640609
 TI    Phosphorylation-dependent human immunodeficiency virus type 1 infection
       and nuclear targeting of viral DNA.
 DT    9604
 AU    Bukrinskaya AG; Ghorpade A; Heinzinger NK; Smithgall TE; Lewis RE;
       Stevenson M; Department of Pathology and Microbiology, University of
       Nebraska; Medical Center, Omaha 68198-5120, USA.
 SO    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):367-71. Unique Identifier :
       AIDSLINE MED/96133938
 AB    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.
 DE    Base Sequence  Cell Compartmentation  Cell Membrane/METABOLISM  Cell
       Nucleus/METABOLISM  DNA Primers/CHEMISTRY  DNA, Viral/*METABOLISM  Gene
       Products, gag/*METABOLISM  Hela Cells  Human  HIV-1/ENZYMOLOGY/*GROWTH &
       DEVELOPMENT/GENETICS  Molecular Sequence Data  Myristates/METABOLISM
       Phosphoproteins/METABOLISM  Phosphorylation  Phosphoserine/METABOLISM
       Phosphotyrosine/METABOLISM  Protein-Serine-Threonine Kinases/ANTAGONISTS
       & INHIB  Protein-Tyrosine Kinase/ANTAGONISTS & INHIB  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Viral Matrix Proteins/*METABOLISM
       Virion/ENZYMOLOGY  *Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

