Mutations of the HIV type 1 V3 loop under selection pressure with neutralizing monoclonal antibody NM-01.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Mutations of the HIV type 1 V3 loop under selection pressure with neutralizing monoclonal antibody NM-01.

AIDS Res Hum Retroviruses. 1997 Oct 10;13(15):1283-90. Unique Identifier : AIDSLINE MED/97479764
Yoshida K; Nakamura M; Ohno T; Department of Microbiology, The Jikei University School of; Medicine, Tokyo, Japan.

Abstract: Variants of human immunodeficiency virus type 1 (HIV-1) were selected for resistance to the neutralizing monoclonal antibody (MAb) NM-01. MAb NM-01 recognizes the center of the third hypervariable domain (V3 loop) of the envelope gp120, and neutralizes diverse HIV-1 strains. In the continuous presence of MAb NM-01, transmission and propagation of molecularly cloned HIV-1 were performed in vitro to isolate escape variants. The polymerase chain reaction-single-strand conformation polymorphism and sequence analyses of these variants indicated that the antigenic change against MAb NM-01 is due to a single base substitution resulting in one amino acid interchange within the recognition site of MAb NM-01 in the V3 loop. Mutational analyses also demonstrated a nonrandom event of variability and the existence of mutational hot spots in the V3 loop. The bias of variability could be interpreted by the specificity of error-prone replication by HIV-1 reverse transcriptase. Furthermore, the results suggest that distribution of mutability might correlate closely with the stability of the secondary structure of RNA encoding the V3 loop region.

Keywords: Antibodies, Monoclonal/IMMUNOLOGY Antigenic Variation/GENETICS Base Composition Base Sequence Cells, Cultured Cloning, Molecular DNA Mutational Analysis DNA, Viral/ANALYSIS Hela Cells Human HIV Antibodies/*IMMUNOLOGY HIV Envelope Protein gp120/*GENETICS/*IMMUNOLOGY HIV Infections/*GENETICS/IMMUNOLOGY HIV-1/*GENETICS/*IMMUNOLOGY HIV-1 Reverse Transcriptase/GENETICS Molecular Sequence Data Molecular Structure Neutralization Tests Plasmids Point Mutation Polymorphism, Single-Stranded Conformational RNA, Viral/CHEMISTRY/GENETICS Support, Non-U.S. Gov't JOURNAL ARTICLE
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M9820725

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