Document 0382
 DOCN  M9620382
 TI    Biological activity of human immunodeficiency virus type 1 Vif requires
       membrane targeting by C-terminal basic domains.
 DT    9602
 AU    Goncalves J; Shi B; Yang X; Gabuzda D; Division of Human Retrovirology,
       Dana-Farber Cancer Institute,; Boston, Massachusetts 02115, USA.
 SO    J Virol. 1995 Nov;69(11):7196-204. Unique Identifier : AIDSLINE
       MED/96013824
 AB    Human immunodeficiency virus type 1 (HIV-1) encodes a Vif protein which
       is important for virus replication and infectivity. Vif is a cytoplasmic
       protein which exists in both membrane-associated and soluble forms. The
       membrane-associated form is an extrinsic membrane protein which is
       tightly associated with the cytoplasmic side of membranes. We have
       analyzed the mechanism of membrane targeting of Vif and its role in
       HIV-1 replication. Mutagenesis studies demonstrate that C-terminal basic
       domains are required for membrane association. Vif mutations which
       disrupt membrane association also inhibit HIV-1 replication, indicating
       that membrane localization of Vif is likely to be required for its
       biological activity in vivo. Membrane binding of Vif is almost
       completely abolished by trypsin treatment of membranes. These results
       demonstrate that membrane localization of Vif requires C-terminal basic
       domains and interaction with a membrane-associated protein(s). This
       interaction may serve to direct Vif to a specific cellular site, since
       immunofluorescence staining and plasma membrane fractionation studies
       show that Vif is localized predominantly to an internal cytoplasmic
       compartment rather than to the plasma membrane. The mechanism of
       membrane targeting of Vif is different in some respects from that of
       other extrinsic membrane proteins, such as Ras, Src, and MARCKS, which
       utilize a basic domain together with a lipid modification for membrane
       targeting. Membrane targeting of Vif is likely to play an important role
       in HIV-1 replication and thus may be a therapeutic target.
 DE    Amino Acid Sequence  Binding Sites  Cell Line  Cell Membrane/PHYSIOLOGY
       Comparative Study  CD4-Positive T-Lymphocytes  Gene Products,
       vif/BIOSYNTHESIS/CHEMISTRY/*METABOLISM  Human
       HIV-1/*PHYSIOLOGY/PATHOGENICITY  Kinetics  Membrane Fusion  Membrane
       Proteins/PHYSIOLOGY  Molecular Sequence Data  Mutagenesis, Site-Directed
       Recombinant Proteins/BIOSYNTHESIS/CHEMISTRY/METABOLISM  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Transfection  *Virus
       Replication  JOURNAL ARTICLE

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