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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Establishment of HIV-1 latency in resting CD4~+ T cells depends on chemokine-induced changes in the actin cytoskeleton
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Establishment of HIV-1 latency in resting CD4~+ T cells depends on chemokine-induced changes in the actin cytoskeleton

机译:在静息CD4〜+ T细胞中HIV-1潜伏期的建立取决于趋化因子诱导的肌动蛋白细胞骨架的变化

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摘要

Eradication of HIV-1 with highly active antiretroviral therapy (HAART) is not possible due to the persistence of long-lived, latently infected resting memory CD4~+ T cells. We now show that HIV-1 latency can be established in resting CD4~+ T cells infected with HIV-1 after exposure to ligands for CCR7 (CCL19), CXCR3 (CXCL9 and CXCL10), and CCR6 (CCL20) but not in unactivated CD4~+ T cells. The mechanism did not involve cell activation or significant changes in gene expression, but was associated with rapid dephosphorylation of cofilin and changes in filamentous actin. Incubation with chemokine before infection led to efficient HIV-1 nuclear localization and integration and this was inhibited by the actin stabilizer jasplakinolide. We propose a unique pathway for establishment of latency by direct HIV-1 infection of resting CD4~+ T cells during normal chemokine-directed recirculation of CD4~+ T cells between blood and tissue.
机译:由于长期存在,潜伏感染的静息记忆CD4〜+ T细胞的持续存在,因此无法使用高活性抗逆转录病毒疗法(HAART)消除HIV-1。我们现在显示,暴露于CCR7(CCL19),CXCR3(CXCL9和CXCL10)和CCR6(CCL20)的配体后,HIV-1潜伏期可以在感染HIV-1的静息CD4〜+ T细胞中建立,而在未激活的CD4中则无法建立〜+ T细胞。该机制不涉及细胞活化或基因表达的显着变化,但与cofilin的快速去磷酸化和丝状肌动蛋白的变化有关。感染前与趋化因子一起温育可导致有效的HIV-1核定位和整合,而肌动蛋白稳定剂jasplakinolide可抑制这种作用。我们提出了一种独特的途径,可以通过在正常的趋化因子指导的血液和组织之间的CD4 ++ T细胞正常再循环过程中,通过静息的CD4 ++ T细胞直接HIV-1感染建立潜伏期。

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    Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia Departments of Immunology, Monash University, Melbourne 3004, Australia Departments of Medicine Monash University, Melbourne 3004, Australia;

    rnDepartments of Medicine Monash University, Melbourne 3004, Australia;

    rnDepartments of Medicine Monash University, Melbourne 3004, Australia;

    rnDepartments of Medicine Monash University, Melbourne 3004, Australia;

    rnDepartments of Medicine Monash University, Melbourne 3004, Australia;

    rnDepartments of Medicine Monash University, Melbourne 3004, Australia;

    rnLaboratoire d'lmmunologie, Centre de Recherche de Centre Hospitalier de L'Universitie de Montreal, Saint-Luc, Quebec, Canada;

    rnLaboratoire d'lmmunologie, Centre de Recherche de Centre Hospitalier de L'Universitie de Montreal, Saint-Luc, Quebec, Canada;

    rnLaboratoire d'lmmunologie, Centre de Recherche de Centre Hospitalier de L'Universitie de Montreal, Saint-Luc, Quebec, Canada;

    rnWestmead Millenium Research Institute, Westmead 2145, Australia;

    rnCentre for Virology, Burnet Institute, Melbourne 3004, Australia;

    rnCentre for Virology, Burnet Institute, Melbourne 3004, Australia;

    rnCentre for Virology, Burnet Institute, Melbourne 3004, Australia Dpartment of Biochemistry and Molecular Biology, Department of Microbiology, Monash University, Clayton 3800, Australia;

    rnWestmead Millenium Research Institute, Westmead 2145, Australia;

    rnDepartments of Immunology, Monash University, Melbourne 3004, Australia Departments of Medicine Monash University, Melbourne 3004, Australia Centre for Virology, Burnet Institute, Melbourne 3004, Australia;

    rnInfectious Diseases Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia Departments of Immunology, Monash University, Melbourne 3004, Australia Centre for Virology, Burnet Institute, Melbourne 3004, Australia;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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