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).