The Ability of Chloroquine To Prevent Tat-Induced Cytokine Secretion by Monocytes Is Implicated in Its In Vivo Anti-Human Immunodeficiency Virus Type 1 Activity

AUTOR(ES)

Rayne, Fabienne

FONTE

American Society for Microbiology

RESUMO

Hydroxychloroquine at 1 μM reduces the load of human immunodeficiency virus type 1 (HIV-1) in patients, whereas chloroquine (CQ) concentrations above 3 μM are required for inhibition of HIV-1 replication in peripheral blood mononuclear cells. Exogenous HIV-1 Tat reaches the cytosol of T cells by using low endosomal pH, and endosome neutralization by CQ prevents Tat from entering and affecting T cells. We show here that 0.6 μM CQ inhibits cytokine secretion induced by Tat in monocytes without affecting lipopolysaccharide-triggered cytokine release. This finding suggests that the in vivo anti-HIV-1 effect of CQ results not from a direct effect on the infected cell but rather from the capacity of CQ to prevent Tat from perturbing the cytokine balance.

Documentos Relacionados

• A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type 1 promoter.
• Cooperative inhibition of NF-kappa B and Tat-induced superactivation of human immunodeficiency virus type 1 long terminal repeat.
• A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat.
• Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro.
• Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein.