       Document 0121
 DOCN  M9620121
 TI    Identification of V3 mutations that can compensate for inactivating
       mutations in C4 of simian immunodeficiency virus.
 DT    9602
 AU    Kirchhoff F; Morrison HG; Desrosiers RC; New England Regional Primate
       Research Center, Harvard Medical; School, Southborough, Massachusetts
       01772-9102, USA.
 SO    Virology. 1995 Oct 20;213(1):179-89. Unique Identifier : AIDSLINE
       MED/96036492
 AB    A valine to isoleucine substitution at position 322 within variable
       region 3 (V3) of envelope of simian immunodeficiency virus was
       previously shown to compensate for an inactivating valine to glycine
       mutation at position 448 in constant region 4 (C4) (Morrison et al.,
       Virology 195, 167-174, 1993). Cloned DNA fragments with inactivating C4
       mutations were combined with complex mixtures of mutant V3 sequences,
       and full length genomes were transfected into COS-1 cells. By
       cocultivating transfected cells with CEM x 174 cells, we were able to
       identify two additional compensatory V3-C4 combinations. Changing 334
       proline to leucine compensated for an inactivating 428 asparagine to
       lysine mutation and changing 324 isoleucine to leucine compensated for
       an inactivating 448 valine to glycine mutation. The double mutants
       replicated efficiently in CEM x 174 cells, rhesus monkey peripheral
       blood mononuclear cells, and the continuously growing rhesus monkey T
       cell line 221. Surprisingly, the 324 I-->L and 33 P-->L mutations by
       themselves impaired SIVmac239 wild-type replication in CEM x 174 cells.
       These results confirm the cooperation between V3 and C4 sequences and
       they define additional specific residues participating in this
       cooperation.
 DE    Amino Acid Sequence  Animal  Base Sequence  Cell Line  Cells, Cultured
       Cercopithecus aethiops  Genes, env/*GENETICS  Kidney/CYTOLOGY/VIROLOGY
       Leukocytes, Mononuclear/VIROLOGY  Macaca mulatta  Microfilament
       Proteins/ANALYSIS  Molecular Sequence Data  Mutagenesis, Site-Directed
       *Mutation  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       SIV/*GENETICS/PHYSIOLOGY  T-Lymphocytes/VIROLOGY  Transfection  Viral
       Envelope Proteins/*GENETICS  Virus Replication/GENETICS  JOURNAL ARTICLE

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

