Immunity to HIV-1 Is Influenced by Continued Natural Exposure to Exogenous Virus

PLoS Pathogens

Vanessa A. York¹  Christian B. Willberg¹  Emily M. Eriksson¹  Douglas F. Nixon¹  Teri J. Liegler²  Robert M. Grant³  Larry A. Bragg³  J. Jeff McConnell³  Fredrick M. Hecht⁴ 

[1] Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America;Division of HIV/AIDS, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America;Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California, United States of America;Positive Health Program, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America

关键词: HIV-1;    T cells;    Cytotoxic T cells;    Immune response;    Viral load;    Proteases;    Highly-active antiretroviral therapy;    Phylogenetic analysis;   

DOI  :  10.1371/journal.ppat.1000185

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-γ enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4+ and CD8+ T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure.

【 授权许可】

CC BY