HMGB1 activates replication of latent HIV-1 in a monocytic cell-line, but inhibits HIV-1 replication in primary macrophages.
High mobility group box protein 1 (HMGB1) is an abundant component of mammalian cells that can be released into extracellular milieu actively or by cells that undergo necrosis. Exposure of inflammatory and endothelial cells to HMGB1 leads to the release of cytokines, including TNF-alpha and IL-6. To evaluate the impact of exogenous HMGB1 on viral replication in HIV-1 infected cells, we studied models of latent and acute infection. Extracellular HMGB1 dose dependently increased HIV-1 replication in the monocytic cells, U1, which is an established model for studying latent HIV-1 infection. Dexamethasone, a known inhibitor of NF-kappaB signaling in U1 cells, inhibited HMGB1-induced stimulation of the viral production. Addition of HMGB1 to primary monocytic cells with active HIV-1 infection elicited the opposite effect, due to suppression of the viral replication. The mechanism of this unexpected finding was explained by an HMGB1-mediated increased release of chemokines (RANTES, MIP-1alpha, and MIP-1beta) that are known to inhibit HIV-1 replication. The stimulatory effect of the HMGB1 was not present when latently infected T-cells (ACH-2) were used as target cells. Our data suggest that extracellular HMGB1 has a dichotomic effect on the HIV-1 infection in monocytes but not in lymphocytes. Both activation of latent HIV-1 infection and inhibition of active replication can thus be seen in vitro.
Nowak
Piotr
P
Division of Clinical Virology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. Piotr.Nowak@labmed.ki.se
Barqasho
Babilonia
B
Treutiger
Carl Johan
CJ
Harris
Helena Erlandsson
HE
Tracey
Kevin J
KJ
Andersson
Jan
J
Sönnerborg
Anders
A
D002470:Cell Survival; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000821:virology*; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D009336:Necrosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D024243:HMGB1 Protein; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha