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Science 24 July 1992:
Vol. 257. no. 5069, pp. 535 - 537
DOI: 10.1126/science.1636088

Articles

Science, Vol 257, Issue 5069, 535-537
Copyright © 1992 by American Association for the Advancement of Science


articles

Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1

SS Hwang, TJ Boyle, HK Lyerly, and BR Cullen

Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.

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.


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