A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages

作者：Zhou Yu; Wang Xu; Liu Manqing; Hu Quan; Song Li; Ye Li; Zhou Dunjin; Ho Wenzhe^*

来源：Immunology, 2010, 131(1): 40-49.

DOI：10.1111/j.1365-2567.2010.03270.x

• CC chemokine
• microRNA
• poly I:C
• tetherin
• type I interferon

P>Toll-like receptor-3 (TLR-3) recognizes double-stranded RNA and induces multiple intracellular events responsible for innate anti-viral immunity against a number of viral infections. Activation of TLR-3 inhibits human immunodeficiency virus (HIV) replication, but the mechanism(s) underlying the action of TLR-3 activation on HIV are largely unknown. Here we demonstrate that treatment of monocyte-derived macrophages with poly I:C, a synthetic ligand for TLR-3, significantly inhibited HIV infection and replication. Investigation of the mechanisms showed that TLR-3 activation resulted in the induction of type I interferon inducible antiviral factors, including APOBEC3G and tetherin, the newly identified anti-HIV cellular proteins. In addition, poly I:C-treated macrophages expressed increased levels of CC chemokines, the ligands for CCR5. Furthermore, TLR-3 activation in macrophages induced the expression of cellular microRNAs (miRNA-28, -125b, -150, -223 and -382), the newly identified intracellular HIV restriction factors. These findings indicate that TLR-3-mediated induction of multiple anti-HIV factors should be beneficial for the treatment of HIV disease where innate immune responses are compromised by the virus.

• 出版日期2010-9