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Journal of Virology, October 2009, p. 10821-10829, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.00839-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Preinfection Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T Lymphocytes Failed To Prevent HIV Type 1 Infection from Strains Genetically Unrelated to Viruses in Long-Term Exposed Partners{triangledown}

Yi Liu,2,{dagger} Amanda Woodward,1,{dagger} Haiying Zhu,1,{dagger} Thomas Andrus,1 John McNevin,4 Jean Lee,4 James I. Mullins,1,2,3 Lawrence Corey,1,2,3,4 M. Juliana McElrath,3,4 and Tuofu Zhu1,2,4*

Departments of Laboratory Medicine,1 Microbiology,2 Medicine, University of Washington, Seattle, Washington,3 Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 981094

Received 24 April 2009/ Accepted 18 July 2009

Understanding the mechanisms underlying potential altered susceptibility to human immunodeficiency virus type 1 (HIV-1) infection in highly exposed seronegative (ES) individuals and the later clinical consequences of breakthrough infection can provide insight into strategies to control HIV-1 with an effective vaccine. From our Seattle ES cohort, we identified one individual (LSC63) who seroconverted after over 2 years of repeated unprotected sexual contact with his HIV-1-infected partner (P63) and other sexual partners of unknown HIV-1 serostatus. The HIV-1 variants infecting LSC63 were genetically unrelated to those sequenced from P63. This may not be surprising, since viral load measurements in P63 were repeatedly below 50 copies/ml, making him an unlikely transmitter. However, broad HIV-1-specific cytotoxic T-lymphocyte (CTL) responses were detected in LSC63 before seroconversion. Compared to those detected after seroconversion, these responses were of lower magnitude and half of them targeted different regions of the viral proteome. Strong HLA-B27-restricted CTLs, which have been associated with disease control, were detected in LSC63 after but not before seroconversion. Furthermore, for the majority of the protein-coding regions of the HIV-1 variants in LSC63 (except gp41, nef, and the 3' half of pol), the genetic distances between the infecting viruses and the viruses to which he was exposed through P63 (termed the exposed virus) were comparable to the distances between random subtype B HIV-1 sequences and the exposed viruses. These results suggest that broad preinfection immune responses were not able to prevent the acquisition of HIV-1 infection in LSC63, even though the infecting viruses were not particularly distant from the viruses that may have elicited these responses.

* Corresponding author. Mailing address: Department of Laboratory Medicine, Box 358070, University of Washington School of Medicine, 960 Republican Street, Seattle, WA 98109. Phone: (206) 732-6079. Fax: (206) 732-6109. E-mail: tzhu{at}u.washington.edu

{triangledown} Published ahead of print on 12 August 2009.

{dagger} These authors contributed equally to this work.

Journal of Virology, October 2009, p. 10821-10829, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.00839-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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