Studies of the conformation-dependent neutralizing epitopes of simian immunodeficiency virus envelope protein.
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.
Javaherian
K
K
Repligen Corporation, Cambridge, Massachusetts 02139.
Langlois
A J
AJ
Montefiori
D C
DC
Kent
K A
KA
Ryan
K A
KA
Wyman
P D
PD
Stott
J
J
Bolognesi
D P
DP
Murphey-Corb
M
M
Larosa
G J
GJ
D000143:Acids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D006031:Glycosylation; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D008251:Macaca; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000143:Acids; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012191:Retroviridae Proteins; C080347:SIV envelope protein gp110; D014759:Viral Envelope Proteins