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Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.

Soriano-Sarabia N, Archin NM, Bateson R, Dahl NP, Crooks AM, Kuruc JD, Garrido C, Margolis DM - PLoS Pathog. (2015)

Bottom Line: Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection.We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo.In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

No MeSH data available.


Related in: MedlinePlus

Vδ2 cells from untreated recently HIV-infected patients express CD4 and CCR5.A) Dot plots from three recently infected patient (VP1, VP2 and VP3) showing surface expression of CD4 and CCR5 on CD3+Vδ2+ cells, and on CD3+Vδ2- cells for comparison. B) Density plots showing the percentage of Vδ2 cells coexpressing CD4 and CCR5 in the same three patients.
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ppat.1005201.g007: Vδ2 cells from untreated recently HIV-infected patients express CD4 and CCR5.A) Dot plots from three recently infected patient (VP1, VP2 and VP3) showing surface expression of CD4 and CCR5 on CD3+Vδ2+ cells, and on CD3+Vδ2- cells for comparison. B) Density plots showing the percentage of Vδ2 cells coexpressing CD4 and CCR5 in the same three patients.

Mentions: Based on these results we hypothesized that immune activation, driven in this instance by HIV infection, might upregulate CD4 expression on Vδ2 cells in vivo. To test this hypothesis we measured surface expression of CD4 and CCR5 expression in Vδ2 cells donated by three viremic patients diagnosed during the acute phase of HIV infection, prior to the initiation of ART (Fig 7). Based on history and diagnostic testing, the estimated date of infection in these patients was less than 23 days prior to sampling. Likely related to the pathological immune activation of acute HIV infection, 9.5%, 15.6% and 15.9% of Vδ2 cells expressed CD4 (Fig 7A), as compared to <0.3% of Vδ2 cells in healthy donors. In addition, we also analyzed the percentage of Vδ2 cells that coexpressed CD4 and CCR5 (Fig 7B). This observation in these unique patients supports our hypothesis that pathological immune activation in early HIV infection promotes the upregulation of CD4 expression in Vδ2 cells, making them targets for HIV infection in vivo.


Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.

Soriano-Sarabia N, Archin NM, Bateson R, Dahl NP, Crooks AM, Kuruc JD, Garrido C, Margolis DM - PLoS Pathog. (2015)

Vδ2 cells from untreated recently HIV-infected patients express CD4 and CCR5.A) Dot plots from three recently infected patient (VP1, VP2 and VP3) showing surface expression of CD4 and CCR5 on CD3+Vδ2+ cells, and on CD3+Vδ2- cells for comparison. B) Density plots showing the percentage of Vδ2 cells coexpressing CD4 and CCR5 in the same three patients.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608739&req=5

ppat.1005201.g007: Vδ2 cells from untreated recently HIV-infected patients express CD4 and CCR5.A) Dot plots from three recently infected patient (VP1, VP2 and VP3) showing surface expression of CD4 and CCR5 on CD3+Vδ2+ cells, and on CD3+Vδ2- cells for comparison. B) Density plots showing the percentage of Vδ2 cells coexpressing CD4 and CCR5 in the same three patients.
Mentions: Based on these results we hypothesized that immune activation, driven in this instance by HIV infection, might upregulate CD4 expression on Vδ2 cells in vivo. To test this hypothesis we measured surface expression of CD4 and CCR5 expression in Vδ2 cells donated by three viremic patients diagnosed during the acute phase of HIV infection, prior to the initiation of ART (Fig 7). Based on history and diagnostic testing, the estimated date of infection in these patients was less than 23 days prior to sampling. Likely related to the pathological immune activation of acute HIV infection, 9.5%, 15.6% and 15.9% of Vδ2 cells expressed CD4 (Fig 7A), as compared to <0.3% of Vδ2 cells in healthy donors. In addition, we also analyzed the percentage of Vδ2 cells that coexpressed CD4 and CCR5 (Fig 7B). This observation in these unique patients supports our hypothesis that pathological immune activation in early HIV infection promotes the upregulation of CD4 expression in Vδ2 cells, making them targets for HIV infection in vivo.

Bottom Line: Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection.We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo.In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

ABSTRACT
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

No MeSH data available.


Related in: MedlinePlus