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The cortical actin determines different susceptibility of naïve and memory CD4+ T cells to HIV-1 cell-to-cell transmission and infection.

Permanyer M, Pauls E, Badia R, Est├ę JA, Ballana E - PLoS ONE (2013)

Bottom Line: Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells.Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell.In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization.

View Article: PubMed Central - PubMed

Affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut├▓noma de Barcelona, Badalona, Spain.

ABSTRACT
Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells. HIV-1 fusion and entry is a dynamic process in which the cytoskeleton plays an important role by allowing virion internalization and uncoating. Here, we evaluate the role of the cortical actin in cell-to-cell transfer of virus antigens and infection of target CD4+ T cells. Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell. Naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells could be phenotypically differentiated by the degree of cortical actin density and their capacity to capture virus. Thus, the higher cortical actin density of memory CD4+ T cells was associated to increased efficiency of HIV-antigen internalization and the establishment of a productive infection. Conversely, the lower cortical actin density in naïve CD4+ T cells restricted viral antigen transfer and consequently HIV-1 infection. In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization.

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Distinct degree of cortical actin polymerization in naïve and memory CD4+ T cells.Resting CD4+ T cells were purified from peripheral blood by negative depletion. Surface expression of CD45RA differentiated between naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells. (a) The F-actin in memory and naïve CD4+ T cells from 3 representative donors were evaluated by co-staining of CD45RA and FITC-labelled phalloidin and assessed by flow cytometry. (b) The MFI of F-actin of naïve and memory CD4+ T cells is plotted. Values are normalized to the memory T cell subset. Mean and SD of 3 different donors is shown (**p<0.005). (c) CD4 and CXCR4 receptor expression in naïve and memory CD4+ T cells from one representative donor is shown.
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pone-0079221-g002: Distinct degree of cortical actin polymerization in naïve and memory CD4+ T cells.Resting CD4+ T cells were purified from peripheral blood by negative depletion. Surface expression of CD45RA differentiated between naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells. (a) The F-actin in memory and naïve CD4+ T cells from 3 representative donors were evaluated by co-staining of CD45RA and FITC-labelled phalloidin and assessed by flow cytometry. (b) The MFI of F-actin of naïve and memory CD4+ T cells is plotted. Values are normalized to the memory T cell subset. Mean and SD of 3 different donors is shown (**p<0.005). (c) CD4 and CXCR4 receptor expression in naïve and memory CD4+ T cells from one representative donor is shown.

Mentions: Several post-entry cellular mechanisms may explain the different susceptibility to HIV infection between na├»ve and memory CD4+ T cell subtypes [6]ÔÇô[8], [39]. Because the cortical actin polymerization modulates the internalization of viral antigens during cell-to-cell contacts, we asked whether differences in cortical actin polymerization in distinct CD4+ T cell subtypes may determine different susceptibilities to infection by regulating the efficiency of viral antigen internalization. Na├»ve and memory CD4+ T cell subpopulations can be identified by the expression of surface CD45RA and CD45RO isoforms respectively. Thus, we performed co-staining of F-actin and surface CD45RA in primary non-stimulated CD4+ T cells to study the cortical actin polymerization of these two T cell subsets. In all donors evaluated, the intensity of the F-actin staining was higher in memory CD4+ T cells (Fig. 2a and 2b), indicating that memory CD4+ T cells display a more polymerized actin cytoskeleton than na├»ve CD4+ T cells. To discard that the different susceptibility to HIV-infection in both T cell subtypes could be determined by differences in the coreceptor expression, we evaluated the expression levels of CD4 and CXCR4 receptors in na├»ve and memory resting CD4+ T cells (Fig. 2c). As expected, we did not observe significant differences in both receptors, consistent with previous reports [6], [10].


The cortical actin determines different susceptibility of naïve and memory CD4+ T cells to HIV-1 cell-to-cell transmission and infection.

Permanyer M, Pauls E, Badia R, Est├ę JA, Ballana E - PLoS ONE (2013)

Distinct degree of cortical actin polymerization in naïve and memory CD4+ T cells.Resting CD4+ T cells were purified from peripheral blood by negative depletion. Surface expression of CD45RA differentiated between naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells. (a) The F-actin in memory and naïve CD4+ T cells from 3 representative donors were evaluated by co-staining of CD45RA and FITC-labelled phalloidin and assessed by flow cytometry. (b) The MFI of F-actin of naïve and memory CD4+ T cells is plotted. Values are normalized to the memory T cell subset. Mean and SD of 3 different donors is shown (**p<0.005). (c) CD4 and CXCR4 receptor expression in naïve and memory CD4+ T cells from one representative donor is shown.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3823590&req=5

pone-0079221-g002: Distinct degree of cortical actin polymerization in naïve and memory CD4+ T cells.Resting CD4+ T cells were purified from peripheral blood by negative depletion. Surface expression of CD45RA differentiated between naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells. (a) The F-actin in memory and naïve CD4+ T cells from 3 representative donors were evaluated by co-staining of CD45RA and FITC-labelled phalloidin and assessed by flow cytometry. (b) The MFI of F-actin of naïve and memory CD4+ T cells is plotted. Values are normalized to the memory T cell subset. Mean and SD of 3 different donors is shown (**p<0.005). (c) CD4 and CXCR4 receptor expression in naïve and memory CD4+ T cells from one representative donor is shown.
Mentions: Several post-entry cellular mechanisms may explain the different susceptibility to HIV infection between na├»ve and memory CD4+ T cell subtypes [6]ÔÇô[8], [39]. Because the cortical actin polymerization modulates the internalization of viral antigens during cell-to-cell contacts, we asked whether differences in cortical actin polymerization in distinct CD4+ T cell subtypes may determine different susceptibilities to infection by regulating the efficiency of viral antigen internalization. Na├»ve and memory CD4+ T cell subpopulations can be identified by the expression of surface CD45RA and CD45RO isoforms respectively. Thus, we performed co-staining of F-actin and surface CD45RA in primary non-stimulated CD4+ T cells to study the cortical actin polymerization of these two T cell subsets. In all donors evaluated, the intensity of the F-actin staining was higher in memory CD4+ T cells (Fig. 2a and 2b), indicating that memory CD4+ T cells display a more polymerized actin cytoskeleton than na├»ve CD4+ T cells. To discard that the different susceptibility to HIV-infection in both T cell subtypes could be determined by differences in the coreceptor expression, we evaluated the expression levels of CD4 and CXCR4 receptors in na├»ve and memory resting CD4+ T cells (Fig. 2c). As expected, we did not observe significant differences in both receptors, consistent with previous reports [6], [10].

Bottom Line: Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells.Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell.In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization.

View Article: PubMed Central - PubMed

Affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Aut├▓noma de Barcelona, Badalona, Spain.

ABSTRACT
Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells. HIV-1 fusion and entry is a dynamic process in which the cytoskeleton plays an important role by allowing virion internalization and uncoating. Here, we evaluate the role of the cortical actin in cell-to-cell transfer of virus antigens and infection of target CD4+ T cells. Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell. Naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells could be phenotypically differentiated by the degree of cortical actin density and their capacity to capture virus. Thus, the higher cortical actin density of memory CD4+ T cells was associated to increased efficiency of HIV-antigen internalization and the establishment of a productive infection. Conversely, the lower cortical actin density in naïve CD4+ T cells restricted viral antigen transfer and consequently HIV-1 infection. In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization.

Show MeSH
Related in: MedlinePlus