Norepinephrine inhibits human immunodeficiency virus type-1 infection through the NF-κB inactivation

Exercise or acute stress can exert significant effects on immune system as well as cardiovascular and respiratory systems through catecholamines. In this study, we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays, NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF-κB-binding sites or cotreatment with H89 (a protein kinase A inhibitor) abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF-κB activity in NE-treated cells. NE increased cytoplasmic levels of IκB-α, a natural inhibitor of NF-κB. Thus, NE apparently inhibits HIV-1 infection, at least in part through NF-κB inactivation.