Mutations of the HIV type 1 V3 loop under selection pressure with neutralizing monoclonal antibody NM-01.
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.
Yoshida
K
K
Department of Microbiology, The Jikei University School of Medicine, Tokyo, Japan.
Nakamura
M
M
Ohno
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D000940:Antigenic Variation / Q000235:genetics; D001482:Base Composition; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009500:Neutralization Tests; D010957:Plasmids; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase