       Document 0724
 DOCN  M95A0724
 TI    Effects of mutations in constant regions 3 and 4 of envelope of simian
       immunodeficiency virus.
 DT    9510
 AU    Morrison HG; Kirchhoff F; Desrosiers RC; New England Regional Primate
       Research Center, Harvard Medical; School, Southborough, Massachusetts
       01772-9102, USA.
 SO    Virology. 1995 Jul 10;210(2):448-55. Unique Identifier : AIDSLINE
       MED/95343557
 AB    Twenty-six mutant forms of simian immunodeficiency virus strain mac239
       were constructed with changes in constant region 4 (C4) of env.
       Twenty-four of these had a single amino acid change, one had changes in
       two amino acids, and one had a deletion of eight amino acids. The
       effects of these mutations on viral replication, gp160 processing, and
       binding of env protein to soluble CD4 receptor were analyzed. The C4
       region was relatively sensitive to sequence changes since only 11 of the
       26 mutants replicated appreciably. Eight of the 15 mutants that were
       replication incompetent exhibited grossly defective processing of the
       gp160 env precursor; these mutations likely resulted in global effects
       on gp160 structure. Six of the replication incompetent mutants exhibited
       normal or near normal gp160 processing and binding of env protein to
       sCD4 and thus were probably blocked at some step subsequent to binding
       of virus to its CD4 receptor. Only one of the C4 mutations, 441W-->R,
       resulted in greatly decreased binding to sCD4 while retaining normal
       processing of gp160. The equivalent residue in HIV-1 has similarly been
       shown previously to be important for binding of HIV-1 to the CD4
       receptor. Since a W-->S mutation at position 441 in C4 of SIVmac239
       affected both gp160 processing and sCD4 binding, it is not clear whether
       the 441 tryptophan is actually important for contacting CD4 or for
       maintaining an appropriate configuration. mutations within a highly
       conserved GGDPE sequence in C3 of SIVmac239 specifically affected CD4
       binding, which is also similar to previous findings with HIV-1. These
       results demonstrate similar sequence requirements in SIVmac and HIV-1
       env for binding C4, but they raise doubts as to whether C4 sequences are
       directly involved in the binding.
 DE    Amino Acid Sequence  Antigens, CD4/METABOLISM  Cell Line  Gene Products,
       env/*GENETICS/METABOLISM  Genes, env/GENETICS  Human  Hybrid Cells  HIV
       Envelope Protein gp120/*GENETICS/METABOLISM  Molecular Sequence Data
       Mutation/*PHYSIOLOGY  Protein Precursors/METABOLISM  Recombinant
       Proteins/METABOLISM  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  SIV/*GENETICS/PHYSIOLOGY  Virus Replication/*GENETICS  JOURNAL
       ARTICLE

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

