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M9490426.TXT
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1994-09-19
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Document 0426
DOCN M9490426
TI Effects of natural sequence variation on recognition by monoclonal
antibodies neutralize simian immunodeficiency virus infectivity.
DT 9411
AU Choi WS; Collignon C; Thiriart C; Burns DP; Stott EJ; Kent KA;
Desrosiers RC; New England Regional Primate Research Center, Harvard
Medical; School, Southborough, Massachusetts 01772-9102.
SO J Virol. 1994 Sep;68(9):5395-402. Unique Identifier : AIDSLINE
MED/94335051
AB The determinants of immune recognition by five monoclonal antibodies
(KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian
immunodeficiency virus infectivity were analyzed. These five
neutralizing monoclonal antibodies were generated to native SIVmac251
envelope glycoprotein expressed by a vaccinia virus recombinant vector.
All five recognize conformational or discontinuous epitopes and require
native antigen for optimal recognition. These monoclonal antibodies also
recognize SIVmac239 gp120, but they do not recognize gp120 of two
natural variants of SIVmac239, 1-12 and 8-22, which evolved during the
course of persistent infection in vivo (D.P.W. Burns and R.C.
Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which
were constructed by exchanging variable regions between SIVmac239 and
variant 1-12 were used to define domains important for recognition.
Radioimmunoprecipitation analysis demonstrated that sequence changes in
variable regions 4 and 5 (V4/V5) were primarily responsible for the loss
of recognition of the 1-12 variant. Site-specific mutants were used to
define precise changes that eliminate recognition by these neutralizing
antibodies. Changing N-409 to D, deletion of KPKE, and deletion of KEQH
in V4 each resulted in loss of recognition by all five monoclonal
antibodies. SIVs with these natural sequence changes are still
replication competent and viable. Changing A-417 to T or A/N-417/418 to
TK in V4 or Q-477 to K in V5 did not alter recognition detectably. These
results define specific, naturally occurring sequence changes in V4 of
SIVmac that result in loss of recognition by one class of SIVmac
neutralizing antibodies.
DE Amino Acid Sequence Animal Antibodies,
Monoclonal/CHEMISTRY/*IMMUNOLOGY Antibodies,
Viral/CHEMISTRY/*IMMUNOLOGY Antibody Specificity Antigenic
Determinants Antigens, CD4/METABOLISM Base Sequence Comparative Study
DNA Primers/CHEMISTRY Human HIV Envelope Protein
gp120/CHEMISTRY/IMMUNOLOGY In Vitro Mice Mice, Inbred BALB C
Molecular Sequence Data Mutagenesis, Site-Directed Neutralization
Tests Protein Conformation Recombinant Proteins Sequence Alignment
Sequence Homology, Amino Acid Simian Acquired Immunodeficiency
Syndrome/IMMUNOLOGY Structure-Activity Relationship Support, U.S.
Gov't, P.H.S. SIV/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).