IDENTIFICATION OF ENVELOPE V3 LOOP AS THE MAJOR DETERMINANT OF CD4 NEUTRALIZATION SENSITIVITY OF HIV-1

被引:116
作者
HWANG, SS
BOYLE, TJ
LYERLY, HK
CULLEN, BR
机构
[1] DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,GENET SECT,DURHAM,NC 27710
[2] DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710
[3] DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710
关键词
D O I
10.1126/science.1636088
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页码:535 / 537
页数:3
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