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Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus.

Willberg CB, McConnell JJ, Eriksson EM, Bragg LA, York VA, Liegler TJ, Hecht FM, Grant RM, Nixon DF - PLoS Pathog. (2008)

Bottom Line: 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.Responses consisted of both CD4(+) and CD8(+) T cell subsets.However, no evidence for systemic super-infection was found in any of the individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA. Chris.Willberg@ndm.ox.ac.uk

ABSTRACT
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-gamma 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.

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Direction of exposure and T cell IFN-γ response correlations.IFN-γ T cell responses from the viremic partner (VP) group were plotted against the corresponding average number of unprotected receptive (A) or insertive (B) anal exposures to a partner's HIV-1. Significant correlations (denoted by *) were determined by two-tailed nonparametric spearmans correlation, spearman r (r), and linear regression analysis was plotted as straight lines.
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ppat-1000185-g003: Direction of exposure and T cell IFN-γ response correlations.IFN-γ T cell responses from the viremic partner (VP) group were plotted against the corresponding average number of unprotected receptive (A) or insertive (B) anal exposures to a partner's HIV-1. Significant correlations (denoted by *) were determined by two-tailed nonparametric spearmans correlation, spearman r (r), and linear regression analysis was plotted as straight lines.

Mentions: The type of exposure was further analyzed in the VP group by assessing the average number of unprotected receptive (Figure 3A) versus insertive (Figure 3B) anal intercourse episodes. All the individuals in this study engaged in both activities. Significant correlations were only seen between the IFN-γ responses and the number of receptive exposures. Again, responses against HIV-1 Protease, RT, Integrase, and Nef derived peptides correlated with the immune response. Gag followed the trend but did not reach significance, while CEF responses showed no correlation. There were no significant correlations between the average number of insertive exposures and IFN-γ responses towards HIV-1 Protease, RT, Integrase and Nef. As expected, data from the NVP group did not show a correlation between the IFN-γ responses and the direction of exposure (data not shown).


Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus.

Willberg CB, McConnell JJ, Eriksson EM, Bragg LA, York VA, Liegler TJ, Hecht FM, Grant RM, Nixon DF - PLoS Pathog. (2008)

Direction of exposure and T cell IFN-γ response correlations.IFN-γ T cell responses from the viremic partner (VP) group were plotted against the corresponding average number of unprotected receptive (A) or insertive (B) anal exposures to a partner's HIV-1. Significant correlations (denoted by *) were determined by two-tailed nonparametric spearmans correlation, spearman r (r), and linear regression analysis was plotted as straight lines.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2562513&req=5

ppat-1000185-g003: Direction of exposure and T cell IFN-γ response correlations.IFN-γ T cell responses from the viremic partner (VP) group were plotted against the corresponding average number of unprotected receptive (A) or insertive (B) anal exposures to a partner's HIV-1. Significant correlations (denoted by *) were determined by two-tailed nonparametric spearmans correlation, spearman r (r), and linear regression analysis was plotted as straight lines.
Mentions: The type of exposure was further analyzed in the VP group by assessing the average number of unprotected receptive (Figure 3A) versus insertive (Figure 3B) anal intercourse episodes. All the individuals in this study engaged in both activities. Significant correlations were only seen between the IFN-γ responses and the number of receptive exposures. Again, responses against HIV-1 Protease, RT, Integrase, and Nef derived peptides correlated with the immune response. Gag followed the trend but did not reach significance, while CEF responses showed no correlation. There were no significant correlations between the average number of insertive exposures and IFN-γ responses towards HIV-1 Protease, RT, Integrase and Nef. As expected, data from the NVP group did not show a correlation between the IFN-γ responses and the direction of exposure (data not shown).

Bottom Line: 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.Responses consisted of both CD4(+) and CD8(+) T cell subsets.However, no evidence for systemic super-infection was found in any of the individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA. Chris.Willberg@ndm.ox.ac.uk

ABSTRACT
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-gamma 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.

Show MeSH
Related in: MedlinePlus