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Journal of Virology, September 2007, p. 9061-9071, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00117-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of Human Immunodeficiency Virus (HIV)-Specific T-Cell Immunity in Control of Dual HIV-1 and HIV-2 Infection

Departments of Pathology,¹ Epidemiology,² Medicine,³ Laboratory Medicine, University of Washington, Seattle, Washington 98195,⁴ Program in Infectious Diseases, Clinical Research Division,⁵ Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,⁶ University of Dakar, Dakar, Senegal⁷

Received 17 January 2007/ Accepted 25 May 2007

Progressive immune dysfunction and AIDS develop in most cases of human immunodeficiency virus type 1 (HIV-1) infection but in only 25 to 30% of persons with HIV-2 infection. However, the natural history and immunologic responses of individuals with dual HIV-1 and HIV-2 infection are largely undefined. Based on our previous findings, we hypothesized that among patients with dual infection the control of HIV-1 is associated with the ability to respond to HIV-2 Gag epitopes and to maintain HIV-specific CD4⁺ T-cell responses. To test this, we compared the HIV-specific ex vivo IFN- enzyme-linked immunospot (ELISPOT) assay responses of 19 dually infected individuals to those of persons infected with HIV-1 or HIV-2 only. Further, we assessed the functional profile of HIV Gag-specific CD4⁺ and CD8⁺ T cells from nine HIV dually infected patients by using a multicolor intracellular cytokine staining assay. As determined by ELISPOT assay, the magnitude and frequency of IFN--secreting T-cell responses to gene products of HIV-1 were higher than those to gene products of HIV-2 (2.64 versus 1.53 log₁₀ IFN- spot-forming cells/10⁶ cells [90% versus 63%, respectively].) Further, HIV-1 Env-, Gag-, and Nef- and HIV-2 Gag-specific responses were common; HIV-2 Nef-specific responses were rare. HIV-specific CD4⁺ T helper responses were detected in nine of nine dually infected subjects, with the majority of these T cells producing gamma interferon (IFN-) and tumor necrosis factor alpha (TNF-) and, to a lesser extent, interleukin-2. The HIV-1 plasma viral load was inversely correlated with HIV-2 Gag-specific IFN--/TNF--secreting CD4⁺ and HIV-2 Gag-specific IFN--secreting CD8⁺ T cells. In conclusion, the T-cell memory responses associated with containment of single HIV-1 and HIV-2 infection play a similar significant role in the immune control of dual HIV-1 and HIV-2 infection.

Published ahead of print on 20 June 2007.