Identification of Envelope V3 Loop as the Major Determinant of CD4 Neutralization Sensitivity of HIV-1

• Published in: Science (American Association for the Advancement of Science) Vol. 257; no. 5069; pp. 535 - 537
• Main Authors: Hwang, Stephen S., Boyle, Terence J., Lyerly, H. Kim, Cullen, Bryan R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 24.07.1992; American Association for the Advancement of Science
• Subjects: AIDS; AIDS/HIV; Amino Acid Sequence; Amino acids; Animals; Biological and medical sciences; CD4 Antigens - immunology; CD4 lymphocytes; Cell Line; Cells, Cultured; Dosage; Fundamental and applied biological sciences. Psychology; Gene Products, gag - immunology; HIV; HIV (Viruses); HIV 1; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; HIV-1 - isolation & purification; human immunodeficiency virus 1; Humans; Infections; Kinetics; Microbiology; Molecular Sequence Data; Neutralization Tests; Proviruses; Proviruses - immunology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; T lymphocytes; T-Lymphocyte Subsets - immunology; Transfection; Tropisms; Virion - immunology; Virions; Virology; Viruses; Virus; HIV-1 virus; Retroviridae; Lentivirinae; Glycoproteins; Human immunodeficiency virus; Soluble form; Virus envelope; Neutralization; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1636088

Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV-IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4-resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms.