Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene.
Transmission and growth of HIV-1 produced from the biologically active clone HTLV-III/HXB2D in the constant presence of a neutralizing antiserum yielded a viral population specifically resistant to neutralization by the same antiserum. Molecular clones MX-1 and -2, containing the entire envelope gene, were obtained from cultures of the resistant variant. The coding regions for the large envelope protein and most of the transmembrane envelope protein of two such clones were substituted for the homologous segment of HXB2D. Infectious viruses from these constructs were also specifically resistant to neutralization by the selecting antiserum. The exchanged fragment contained only one base change, resulting in an Ala----Thr replacement at position 582. When this substitution was introduced into HXB2D it conferred the resistant phenotype. Thus, small differences may be selected for in vivo by the host immune response and result in relatively large differences in susceptibility of the virus to such a response.
Reitz
M S
MS
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Wilson
C
C
Naugle
C
C
Gallo
R C
RC
Robert-Guroff
M
M
D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D006678:HIV / Q000235:genetics* / Q000276:immunology; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007700:Kinetics; D009154:Mutation; D009500:Neutralization Tests; D009693:Nucleic Acid Hybridization; D011533:Proviruses / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics*
D000914:Antibodies, Viral; D003062:Codon; D004279:DNA, Viral; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007106:Immune Sera; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D013912:Threonine; D004262:DNA Restriction Enzymes