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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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Responses to HIV-1 peptides and the CEF pool.A) Percentage of individuals making responses from either group: solid bars indicate the viremic partner group and open bars represent the non-viremic partner group. There was a significant difference in the number of individuals responding to Protease and Integrase peptide pools (p = 0.04 and p = 0.002 respectively), as determined by Fishers exact test. No difference was seen for any other stimuli. B) Magnitude of IFN-γ T cell responses to the HIV-1 or CEF peptide pools, and the total cumulative anti-HIV-1 response. Responses from individuals within the viremic partner group (closed symbols) and individuals within the non-viremic partner group (open symbols) showed significant differences for Protease, RT, Integrase and the total cumulative anti-HIV-1 response, *p<0.001 and **p = 0.0274 respectively. The median of each group is plotted as a horizontal line.
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ppat-1000185-g001: Responses to HIV-1 peptides and the CEF pool.A) Percentage of individuals making responses from either group: solid bars indicate the viremic partner group and open bars represent the non-viremic partner group. There was a significant difference in the number of individuals responding to Protease and Integrase peptide pools (p = 0.04 and p = 0.002 respectively), as determined by Fishers exact test. No difference was seen for any other stimuli. B) Magnitude of IFN-γ T cell responses to the HIV-1 or CEF peptide pools, and the total cumulative anti-HIV-1 response. Responses from individuals within the viremic partner group (closed symbols) and individuals within the non-viremic partner group (open symbols) showed significant differences for Protease, RT, Integrase and the total cumulative anti-HIV-1 response, *p<0.001 and **p = 0.0274 respectively. The median of each group is plotted as a horizontal line.

Mentions: Analysis of T cell IFN-γ responses revealed significantly more individuals from the VP group made responses (as defined in the materials and methods section) to HIV-1 Protease and Integrase peptides, compared to individuals with the NVP group (Figure 1A). However, there was no difference in the percentage of individuals from each group making responses to HIV-1 Gag, Reverse Transcriptase (RT), Nef, or CEF. Further analysis of the individuals who made responses revealed that there was no significant difference in the magnitude of the responses made to either of these proteins (Figure 1B). However, Protease, RT, and Integrase (p<0.001) responses were significantly higher in the VP group compared to the NVP group. Overall, there was a trend towards a higher magnitude of response to HIV-1 Gag, Protease, Integrase and Nef by individuals with viremic partners (VP group). Moreover, cumulatively there was a significantly higher anti-HIV-1 T cell response made by the VP group (p = 0.0274).


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)

Responses to HIV-1 peptides and the CEF pool.A) Percentage of individuals making responses from either group: solid bars indicate the viremic partner group and open bars represent the non-viremic partner group. There was a significant difference in the number of individuals responding to Protease and Integrase peptide pools (p = 0.04 and p = 0.002 respectively), as determined by Fishers exact test. No difference was seen for any other stimuli. B) Magnitude of IFN-γ T cell responses to the HIV-1 or CEF peptide pools, and the total cumulative anti-HIV-1 response. Responses from individuals within the viremic partner group (closed symbols) and individuals within the non-viremic partner group (open symbols) showed significant differences for Protease, RT, Integrase and the total cumulative anti-HIV-1 response, *p<0.001 and **p = 0.0274 respectively. The median of each group is plotted as a horizontal line.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1000185-g001: Responses to HIV-1 peptides and the CEF pool.A) Percentage of individuals making responses from either group: solid bars indicate the viremic partner group and open bars represent the non-viremic partner group. There was a significant difference in the number of individuals responding to Protease and Integrase peptide pools (p = 0.04 and p = 0.002 respectively), as determined by Fishers exact test. No difference was seen for any other stimuli. B) Magnitude of IFN-γ T cell responses to the HIV-1 or CEF peptide pools, and the total cumulative anti-HIV-1 response. Responses from individuals within the viremic partner group (closed symbols) and individuals within the non-viremic partner group (open symbols) showed significant differences for Protease, RT, Integrase and the total cumulative anti-HIV-1 response, *p<0.001 and **p = 0.0274 respectively. The median of each group is plotted as a horizontal line.
Mentions: Analysis of T cell IFN-γ responses revealed significantly more individuals from the VP group made responses (as defined in the materials and methods section) to HIV-1 Protease and Integrase peptides, compared to individuals with the NVP group (Figure 1A). However, there was no difference in the percentage of individuals from each group making responses to HIV-1 Gag, Reverse Transcriptase (RT), Nef, or CEF. Further analysis of the individuals who made responses revealed that there was no significant difference in the magnitude of the responses made to either of these proteins (Figure 1B). However, Protease, RT, and Integrase (p<0.001) responses were significantly higher in the VP group compared to the NVP group. Overall, there was a trend towards a higher magnitude of response to HIV-1 Gag, Protease, Integrase and Nef by individuals with viremic partners (VP group). Moreover, cumulatively there was a significantly higher anti-HIV-1 T cell response made by the VP group (p = 0.0274).

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