CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency.
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.
Saleh
Suha
S
Departments of Medicine, Alfred Hospital, Melbourne, Australia.
Solomon
Ajantha
A
Wightman
Fiona
F
Xhilaga
Miranda
M
Cameron
Paul U
PU
Lewin
Sharon R
SR
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D054415:Chemokine CCL19 / Q000494:pharmacology*; D054421:Chemokine CCL21 / Q000494:pharmacology*; D015658:HIV Infections / Q000209:etiology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007156:Immunologic Memory; D054400:Receptors, CCR7; D017735:Virus Latency
D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7