Type-specific neutralizing determinant in the SIVmac transmembrane protein.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Type-specific neutralizing determinant in the SIVmac transmembrane protein.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:25 (abstract no. 9). Unique Identifier : AIDSLINE PRIM8/900009
Kodama T; Burns D; Silva D; di Marzo Veronese F; Desrosiers R; Department of Microbiology and Molecular Genetics, New England; Regional Primate Research Center, Harvard Medical School,; Southborough, MA, USA

Abstract: Monoclonal antibody SF8/5E11, which recognizes the transmembrane protein (TMP) of simian immunodeficiency virus of macaque monkeys (SIVmac), displayed strict type-specificity. It reacted with cloned and uncloned SIVmac251 but not with cloned SIVmac142 and SIVmac239 on immunoblots. This monoclonal antibody neutralized infection by cloned, cell free SIVmac251 and inhibited formation of syncytia by cloned SIVmac251 infected cells. These activities were specific to cloned SIVmac251 and did not occur with the other viruses. Thus, the mAb recognizes a neutralizing epitope within a variable region of the TMP of SIVmac. Sequence comparison of the three clones and site specific mutagenesis revealed that TMP amino acids 106-110 (Asp-Trp-Asn-Asn-Asp) determined the type-specificity of the monoclonal antibody. This type-specific neutralizing determinant is located within a variable region of SIVmac and HIV-2 which includes conserved, clustered sites for N-linked glycosylation. The determinant corresponds exactly to a variable weak neutralizing epitope in the HIV-1 TMP which also includes conserved, clustered sites for N-linked glycosylation. Thus, the location of at least one neutralizing epitope appears to be common to both SIVmac and HIV-1. Furthermore, we observed genetic variation in this neutralizing determinant following infection of a rhesus monkey with molecularly cloned SIVmac239; variant forms of the type-specific, neutralizing determinant thus accumulated during persistent infection in vivo. Our results suggest a role for this determinant in the viral entry process. Selective pressure from the host immune response may result in sequence variation in this neutralizing determinant.

Keywords: Amino Acid Sequence Animal Antibodies, Monoclonal/IMMUNOLOGY Antigens, Viral/*IMMUNOLOGY Cytopathogenic Effect, Viral Epitopes Glycosylation HIV-1/IMMUNOLOGY HIV-2/IMMUNOLOGY Immunoglobulin Variable Region/IMMUNOLOGY Macaca mulatta Molecular Sequence Data Mutagenesis, Site-Directed Neutralization Tests SIV/GROWTH & DEVELOPMENT/*IMMUNOLOGY Viral Envelope Proteins/GENETICS/*IMMUNOLOGY ABSTRACT
910730
M9170985

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