Open AccessEstablishment of HIV-1 latency in resting CD4 + T cells depends on chemokine-induced changes in the actin cytoskeleton
Author(s) -
Paul Cameron,
Suha Saleh,
Georgina Sallmann,
Ajantha Solomon,
Fiona Wightman,
Vanessa A. Evans,
Geneviève Boucher,
Elias K. Haddad,
RafickPierre Sékaly,
Andrew N. Harman,
Jenny L. Anderson,
K.L. Jones,
Johnson Mak,
Anthony L. Cunningham,
Anthony Jaworowski,
Sharon R. Lewin
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1002894107
Subject(s) - cofilin , cxcl10 , microbiology and biotechnology , ccl20 , c c chemokine receptor type 6 , actin , biology , chemokine , ccl5 , ccl19 , cytoskeleton , cxcl9 , actin cytoskeleton , chemokine receptor , t cell , immunology , cell , il 2 receptor , inflammation , biochemistry , immune system
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.