Journal Article

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

Solomon, Ajantha, Evans, Vanessa A, Sallmann, Georgina, Saleh, Suha, Wightman, Fiona, Mak, Johnson, Boucher, Genevieve, Sekaly, Rafick-Pierre, Lewin, Sharon R, Cunningham, Anthony L, Haddad, Elias K, Jaworowski, Anthony, Cameron, Paul U, Jones, Kate L, Anderson, Jenny L, Harman, Andrew N

2010

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Actin / Actins / Actins - metabolism / Antiretroviral agents / Antiretroviral drugs / Biochemistry / Biological Sciences / Blood / CC chemokine receptors / CCL19 protein / CCL20 protein / CCR6 protein / CCR6 receptor / CCR7 protein / CCR7 receptor / CD4 antigen / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - virology / Cell activation / Cell nucleus / Cell Nucleus - immunology / chemokine CCL19 / chemokine CCL20 / chemokine CXCL10 / chemokine CXCL9 / Chemokine receptors / Chemokines / Chemokines - immunology / Chemokines - pharmacology / Cofilin / Cultured cells / CXCL10 protein / CXCR3 protein / CXCR3 receptor / Cytokines / Cytoskeleton / Cytoskeleton - metabolism / Dephosphorylation / Gene expression / gene expression regulation / highly active antiretroviral therapy / HIV / HIV 1 / HIV infections / HIV Infections - immunology / HIV-1 - physiology / Human immunodeficiency virus / Human immunodeficiency virus 1 / Humans / Immunological memory / Infection / Infections / Integration / Jasplakinolide / Latent infection / ligands / Lymphocytes / Lymphocytes T / Memory cells / microfilaments / Phosphorylation / Receptors, Chemokine - immunology / T cell receptors / therapeutics / Virus Integration - drug effects / Virus Integration - immunology / Virus Internalization / Virus Latency - immunology / Virus Replication / Viruses