Document 0100 DOCN M9460100 TI Studies of the conformation-dependent neutralizing epitopes of simian immunodeficiency virus envelope protein. DT 9404 AU Javaherian K; Langlois AJ; Montefiori DC; Kent KA; Ryan KA; Wyman PD; Stott J; Bolognesi DP; Murphey-Corb M; Larosa GJ; Repligen Corporation, Cambridge, Massachusetts 02139. SO J Virol. 1994 Apr;68(4):2624-31. Unique Identifier : AIDSLINE MED/94187104 AB It has been shown previously that the major neutralizing epitopes in simian immunodeficiency virus (SIV) are discontinuous and conformation dependent and that the V3 loop, in contrast to that of human immunodeficiency virus (HIV) type 1, does not by itself elicit neutralizing antibodies (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 89:1418-1422, 1992). We now present data showing that on the basis of fractionation of infected macaque sera, protease digestion of the envelope, and binding properties of two neutralizing monoclonal antibodies to SIV and SIV-HIV chimeric envelope proteins, changes in V3 can disrupt the conformation-dependent neutralization region. The chimeric protein did not produce significant neutralizing antibodies against either SIV or HIV. We also report that neutralizing antibodies elicited by recombinant SIV envelope proteins of mac251 and B670 isolates cross-neutralize. Finally, we show that deglycosylation of the SIV envelope results in a molecule which binds neither soluble CD4 nor the neutralizing monoclonal antibodies being investigated here and does not elicit sera with a significant neutralizing titer. DE Acids/PHARMACOLOGY Amino Acid Sequence Animal Antibodies, Monoclonal/IMMUNOLOGY Antibodies, Viral/IMMUNOLOGY Antigenic Determinants/*IMMUNOLOGY Antigens, CD4/METABOLISM Antigens, Viral/*IMMUNOLOGY Chimeric Proteins/IMMUNOLOGY Cross Reactions Glycosylation Guinea Pigs HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY Macaca Molecular Sequence Data Neutralization Tests Peptide Fragments/IMMUNOLOGY Protein Binding Protein Conformation Protein Processing, Post-Translational Retroviridae Proteins/GENETICS/*IMMUNOLOGY Support, U.S. Gov't, P.H.S. SIV/*IMMUNOLOGY Viral Envelope Proteins/GENETICS/*IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).