Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton

Paul U Cameron, Suha Saleh, Georgina Sallmann, Ajantha Solomon, Fiona Wightman, Vanessa A Evans, Genevieve Boucher, Elias K Haddad, Rafick-Pierre Sekaly, Andrew N Harman, Jenny L Anderson, Kate L Jones, Johnson Mak, Anthony L Cunningham, Anthony Jaworowski, Sharon R Lewin
Proceedings of the National Academy of Sciences of the United States of America 2010 September 28, 107 (39): 16934-9
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.

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