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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4161-4164.
Prepublished online as a Blood First Edition Paper on September 19, 2007; DOI 10.1182/blood-2007-06-097907.


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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

Brief Report

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 Saleh1, Ajantha Solomon1, Fiona Wightman1, Miranda Xhilaga1, Paul U. Cameron1,3, and Sharon R. Lewin1,3

Departments of1 Medicine and 2 Immunology, Monash University, Melbourne; and 3 Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia

Latent HIV-1 infection of resting memory CD4+ T cells represents the major barrier to HIV-1 eradication. To determine whether the CCR7 ligands involved in lymphocyte migration can alter HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells after incubation with the chemokines CCL19 and CCL21. Incubation with CCL19 or CCL21 did not alter markers of T-cell activation or proliferation. However, after HIV-1 infection of CCL19- or CCL21-treated CD4+ T-cells, we observed low-level HIV-1 production but high concentrations of integrated HIV-1 DNA, approaching that seen in mitogen-stimulated T-cell blasts. Restimulation of CCL19-treated infected CD4+ T cells resulted in virus production consistent with establishment of postintegration 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 with which to study HIV-1 latency in vitro.


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