Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals

被引:66
作者
Zhu, TF
Corey, L
Hwangbo, Y
Lee, JM
Learn, GH
Mullins, JI
McElrath, MJ
机构
[1] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA
[3] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA
[4] Fred Hutchinson Canc Res Ctr, Program Infect Dis, Seattle, WA 98109 USA
基金
英国惠康基金;
关键词
D O I
10.1128/JVI.77.11.6108-6116.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Some individuals remain inexplicably seronegative and lack evidence for human immunodeficiency virus type 1 (HIV-1) infection by conventional serologic or virologic testing despite repeated high-risk virus exposures. Here, we examined 10 exposed seronegative (ES) individuals exhibiting HIV-1-specific cytotoxicity for the presence of HIV-1. We discovered HIV-1 DNA in resting CD4(+) T cells (mean, 0.05 +/- 0.01 copies per million cells) at multiple visits spanning 69 to 130 weeks in two ES individuals at levels that were on average 10(4)- to 10(6)-fold lower than those of other HIV-1-infected populations reported. Sequences of HIV-1 envelope and gag genes remained markedly homogeneous, indicating little to undetectable virus replication. These results provide the evidence for HIV-1 infection in ES individuals below the detection limit of standard assays, suggesting that extraordinary control of infection can occur. The two HIV-infected ES individuals remained healthy and were not superinfected with other HIV-1 strains despite continued high-risk sexual exposures to multiple HIV-infected partners. Understanding the mechanisms that confer diminished replicative capacity of HIV-1 in these hosts is paramount to developing strategies for protection against and control of HIV-1 infection.
引用
收藏
页码:6108 / 6116
页数:9
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