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Journal of Virology, June 2003, p. 6108-6116, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6108-6116.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Persistence of Extraordinarily Low Levels of Genetically Homogeneous Human Immunodeficiency Virus Type 1 in Exposed Seronegative Individuals

Tuofu Zhu,1,2* Lawrence Corey,1,2,3,4 Yon Hwangbo,1 Jean M. Lee,1 Gerald H. Learn,2 James I. Mullins,1,2 and M. Juliana McElrath1,3,4

Departments of Laboratory Medicine,1 Microbiology,2 and Medicine, University of Washington School of Medicine, Seattle, Washington 98195,3 Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 981094

Received 1 July 2002/ Accepted 27 September 2002

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 104- to 106-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.

* Corresponding author. Mailing address: Department of Laboratory Medicine, University of Washington School of Medicine, Box 358070, 1959 N.E. Pacific St., Seattle, WA 98195-8070. Phone: (206) 732-6079. Fax: (206) 732-6055. E-mail: tzhu{at}u.washington.edu.

Journal of Virology, June 2003, p. 6108-6116, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6108-6116.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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