Submitted June 26, 2007
Accepted September 10, 2007
CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T-cells to HIV-1 infection: a novel model of HIV-1 latency
Suha Saleh, Ajantha Solomon, Fiona Wightman, Miranda Xhilaga, Paul U Cameron, and Sharon R. Lewin*
Department of Medicine, Monash University, Melbourne, Victoria, Australia
Department of Immunology, Monash University, Melbourne, Victoria, Australia
Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia
* Corresponding author; email: s.lewin{at}alfred.org.au.
Latent HIV-1 infection of resting memory CD4+ T-cells represents the major barrier to HIV-1 eradication. To determine if the CCR7 ligands involved in lymphocyte migration can alter HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells following incubation with the chemokines CCL19 and CCL21. Incubation with CCL19 or CCL21 did not alter markers of T-cell activation or proliferation. However, following HIV-1 infection of CCL19- or CCL21-treated CD4+ T-cells, we observed low level HIV-1 production but high concentration of integrated HIV-1 DNA, approaching that seen in mitogen stimulated T-cell blasts. Re-stimulation of CCL19-treated infected CD4+ T-cells resulted in virus production consistent with establishment of post-integration latency. CCR7 ligands facilitate efficient entry of HIV-1 into resting CD4+ T cells. These studies demonstrate a unique action of the chemokines CCL19 and CCL21 and provide a novel model to study HIV-1 latency in vitro.
