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M9620121.TXT
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1996-02-26
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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).