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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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IFN-γ responses are derived from both CD4+and CD8+ T cells. CD4+ (open boxes) and CD8+ (shaded boxes) T cell IFN-γ responses towards HIV-1 derived peptide pools Gag, Protease, RT, Integrase and Nef, plus the cumulative anti-HIV-1 response and a SEB positive control. No significant difference was observed between the two T cell subsets (n = 5).
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ppat-1000185-g004: IFN-γ responses are derived from both CD4+and CD8+ T cells. CD4+ (open boxes) and CD8+ (shaded boxes) T cell IFN-γ responses towards HIV-1 derived peptide pools Gag, Protease, RT, Integrase and Nef, plus the cumulative anti-HIV-1 response and a SEB positive control. No significant difference was observed between the two T cell subsets (n = 5).

Mentions: To determine which T cell subset was responsible for the IFN-γ response detected in the ELISpot assay, individuals from the viremic partner group (n = 7) were screened by flow cytometry. Individuals were tested using the same 15mer peptide pools used in the ELISpot assay. Both CD4+ and CD8+ T cell subsets produced IFN-γ in response to all the HIV-1 peptide pools (Figure 4). However, no significant difference between the two subsets was seen, although there was a trend towards the CD8+ T cell subset.


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)

IFN-γ responses are derived from both CD4+and CD8+ T cells. CD4+ (open boxes) and CD8+ (shaded boxes) T cell IFN-γ responses towards HIV-1 derived peptide pools Gag, Protease, RT, Integrase and Nef, plus the cumulative anti-HIV-1 response and a SEB positive control. No significant difference was observed between the two T cell subsets (n = 5).
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1000185-g004: IFN-γ responses are derived from both CD4+and CD8+ T cells. CD4+ (open boxes) and CD8+ (shaded boxes) T cell IFN-γ responses towards HIV-1 derived peptide pools Gag, Protease, RT, Integrase and Nef, plus the cumulative anti-HIV-1 response and a SEB positive control. No significant difference was observed between the two T cell subsets (n = 5).
Mentions: To determine which T cell subset was responsible for the IFN-γ response detected in the ELISpot assay, individuals from the viremic partner group (n = 7) were screened by flow cytometry. Individuals were tested using the same 15mer peptide pools used in the ELISpot assay. Both CD4+ and CD8+ T cell subsets produced IFN-γ in response to all the HIV-1 peptide pools (Figure 4). However, no significant difference between the two subsets was seen, although there was a trend towards the CD8+ T cell subset.

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