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Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.

Kiene M, Rethi B, Jansson M, Dillon S, Lee E, Lantto R, Wilson C, Pöhlmann S, Chiodi F - PLoS ONE (2014)

Bottom Line: Here, we show that GPR15 expression in CD4(+) T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls.Up-regulation of GPR15 expression on CD4(+) T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4(+) T cells.These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+) T cells to HIV infection and target cell availability in the gut in some infected individuals.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Background: Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+) T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection.

Results: Here, we show that GPR15 expression in CD4(+) T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4(+) T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4(+) T cells.

Conclusion: These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+) T cells to HIV infection and target cell availability in the gut in some infected individuals.

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Related in: MedlinePlus

HIV-1 infection increases GPR15 expression on infected cells.The PM1 T cell line was infected with three different primary HIV-1 isolates the multitropic isolates 25 and 4052 and the R5-tropic 2195 for 3 days and afterwards stained for GPR15 surface expression and intracellular p24. The percent of uninfected (p24−) or infected (p24+)cells expressing GPR15 is shown.
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pone-0088195-g002: HIV-1 infection increases GPR15 expression on infected cells.The PM1 T cell line was infected with three different primary HIV-1 isolates the multitropic isolates 25 and 4052 and the R5-tropic 2195 for 3 days and afterwards stained for GPR15 surface expression and intracellular p24. The percent of uninfected (p24−) or infected (p24+)cells expressing GPR15 is shown.

Mentions: To investigate if HIV-1 infection can up-regulate GPR15 surface expression we chose the PM1 T cell line as a model system [28].. No appreciable change in total GPR15 expression was observed on non-infected cells upon infection with the multitropic HIV-1 isolates 25, 4054 and the R5 tropic isolate 2195. All three isolates infected PM1 cells with comparable efficiency. For all three virus isolates the expression of GPR15 was markedly higher on infected compared to uninfected PM1 cells, as determined by co-staining of intracellular HIV-1 p24 (Figure 2), suggesting that HIV-1 infection up-regulates GPR15 expression.


Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.

Kiene M, Rethi B, Jansson M, Dillon S, Lee E, Lantto R, Wilson C, Pöhlmann S, Chiodi F - PLoS ONE (2014)

HIV-1 infection increases GPR15 expression on infected cells.The PM1 T cell line was infected with three different primary HIV-1 isolates the multitropic isolates 25 and 4052 and the R5-tropic 2195 for 3 days and afterwards stained for GPR15 surface expression and intracellular p24. The percent of uninfected (p24−) or infected (p24+)cells expressing GPR15 is shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928197&req=5

pone-0088195-g002: HIV-1 infection increases GPR15 expression on infected cells.The PM1 T cell line was infected with three different primary HIV-1 isolates the multitropic isolates 25 and 4052 and the R5-tropic 2195 for 3 days and afterwards stained for GPR15 surface expression and intracellular p24. The percent of uninfected (p24−) or infected (p24+)cells expressing GPR15 is shown.
Mentions: To investigate if HIV-1 infection can up-regulate GPR15 surface expression we chose the PM1 T cell line as a model system [28].. No appreciable change in total GPR15 expression was observed on non-infected cells upon infection with the multitropic HIV-1 isolates 25, 4054 and the R5 tropic isolate 2195. All three isolates infected PM1 cells with comparable efficiency. For all three virus isolates the expression of GPR15 was markedly higher on infected compared to uninfected PM1 cells, as determined by co-staining of intracellular HIV-1 p24 (Figure 2), suggesting that HIV-1 infection up-regulates GPR15 expression.

Bottom Line: Here, we show that GPR15 expression in CD4(+) T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls.Up-regulation of GPR15 expression on CD4(+) T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4(+) T cells.These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+) T cells to HIV infection and target cell availability in the gut in some infected individuals.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Background: Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+) T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection.

Results: Here, we show that GPR15 expression in CD4(+) T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4(+) T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4(+) T cells.

Conclusion: These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+) T cells to HIV infection and target cell availability in the gut in some infected individuals.

Show MeSH
Related in: MedlinePlus