Limits...
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

Frequency of replication-competent HIV expressed as infectious units per million (IUPM) cells.A) Comparison between the frequency of infection within isolated Vδ2 cells between patients treated in the acute HIV infection (AHI) and patients treated in the chronic HIV infection (CHI). B) Point estimate (95% CI) of the frequency of infection in isolated Vδ2 cells (circles) and resting CD4+ T (r-CD4) cells (triangles) in individual patients treated in AHI (left panel) or treated in CHI (right panel). Open symbols means HIVp24 was below the limit of detection, that was <10.67 for Vδ2 cells in patient A6, <0.1 for r-CD4 cells in patient A7, and <31.9 for Vδ2 cells in patient C3. C) Comparison of the point estimate of the frequency of infection between Vδ2 cells and r-CD4 cells in patients treated in AHI (left panel) and patients treated in CHI (right panel). p> 0.05, Wilcoxon signed-ranked test.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608739&req=5

ppat.1005201.g004: Frequency of replication-competent HIV expressed as infectious units per million (IUPM) cells.A) Comparison between the frequency of infection within isolated Vδ2 cells between patients treated in the acute HIV infection (AHI) and patients treated in the chronic HIV infection (CHI). B) Point estimate (95% CI) of the frequency of infection in isolated Vδ2 cells (circles) and resting CD4+ T (r-CD4) cells (triangles) in individual patients treated in AHI (left panel) or treated in CHI (right panel). Open symbols means HIVp24 was below the limit of detection, that was <10.67 for Vδ2 cells in patient A6, <0.1 for r-CD4 cells in patient A7, and <31.9 for Vδ2 cells in patient C3. C) Comparison of the point estimate of the frequency of infection between Vδ2 cells and r-CD4 cells in patients treated in AHI (left panel) and patients treated in CHI (right panel). p> 0.05, Wilcoxon signed-ranked test.

Mentions: Next, we calculated the frequency of infection expressed as infectious units per million (IUPM) isolated Vδ2 cells in 14 patients with available cell dilutions (seven AHI and seven CHI) (Fig 4A). In addition, IUPM r-CD4 cells from the same patients were calculated to compare both cell populations. Percentages of r-CD4 cells, number of cells cultured and total number of positive and total cells assayed are shown in Table 2. As expected, the confidence interval for Vδ2 cells was much greater than for r-CD4 cells due to the lower number of Vδ2 cells assayed and therefore the estimation of the frequency of infection is less accurate (Fig 4B). However, we could not detect statistical differences when IUPM Vδ2 cells were compared to IUPM r-CD4 cells, suggesting that despite the inaccuracy of the co-culture system, Vδ2 cells may be frequently latently infected.


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)

Frequency of replication-competent HIV expressed as infectious units per million (IUPM) cells.A) Comparison between the frequency of infection within isolated Vδ2 cells between patients treated in the acute HIV infection (AHI) and patients treated in the chronic HIV infection (CHI). B) Point estimate (95% CI) of the frequency of infection in isolated Vδ2 cells (circles) and resting CD4+ T (r-CD4) cells (triangles) in individual patients treated in AHI (left panel) or treated in CHI (right panel). Open symbols means HIVp24 was below the limit of detection, that was <10.67 for Vδ2 cells in patient A6, <0.1 for r-CD4 cells in patient A7, and <31.9 for Vδ2 cells in patient C3. C) Comparison of the point estimate of the frequency of infection between Vδ2 cells and r-CD4 cells in patients treated in AHI (left panel) and patients treated in CHI (right panel). p> 0.05, Wilcoxon signed-ranked test.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005201.g004: Frequency of replication-competent HIV expressed as infectious units per million (IUPM) cells.A) Comparison between the frequency of infection within isolated Vδ2 cells between patients treated in the acute HIV infection (AHI) and patients treated in the chronic HIV infection (CHI). B) Point estimate (95% CI) of the frequency of infection in isolated Vδ2 cells (circles) and resting CD4+ T (r-CD4) cells (triangles) in individual patients treated in AHI (left panel) or treated in CHI (right panel). Open symbols means HIVp24 was below the limit of detection, that was <10.67 for Vδ2 cells in patient A6, <0.1 for r-CD4 cells in patient A7, and <31.9 for Vδ2 cells in patient C3. C) Comparison of the point estimate of the frequency of infection between Vδ2 cells and r-CD4 cells in patients treated in AHI (left panel) and patients treated in CHI (right panel). p> 0.05, Wilcoxon signed-ranked test.
Mentions: Next, we calculated the frequency of infection expressed as infectious units per million (IUPM) isolated Vδ2 cells in 14 patients with available cell dilutions (seven AHI and seven CHI) (Fig 4A). In addition, IUPM r-CD4 cells from the same patients were calculated to compare both cell populations. Percentages of r-CD4 cells, number of cells cultured and total number of positive and total cells assayed are shown in Table 2. As expected, the confidence interval for Vδ2 cells was much greater than for r-CD4 cells due to the lower number of Vδ2 cells assayed and therefore the estimation of the frequency of infection is less accurate (Fig 4B). However, we could not detect statistical differences when IUPM Vδ2 cells were compared to IUPM r-CD4 cells, suggesting that despite the inaccuracy of the co-culture system, Vδ2 cells may be frequently latently infected.

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