a role for microrna-155 modulation in the anti-hiv-1 effects of toll-like receptor 3 stimulation in macrophages的微rna - 155调制作用anti-hiv-1 toll样受体3刺激巨噬细胞的影响.pdfVIP

A Role for microRNA-155 Modulation in the Anti-HIV-1 Effects of Toll-Like Receptor 3 Stimulation in Macrophages 1 1 1 1 ´ 1,2 Gokul Swaminathan , Fiorella Rossi , Luz-Jeannette Sierra , Archana Gupta , Sonia Navas-Martın , ´ ´ 1,2* Julio Martın-Garcıa 1 Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America Abstract HIV-1 infection of macrophages plays a key role in viral pathogenesis and progression to AIDS. Polyinosine-polycytidylic acid (poly(I:C); a synthetic analog of dsRNA) and bacterial lipopolysaccharide (LPS), the ligands for Toll-like receptors (TLR) TLR3 and TLR4, respectively, are known to decrease HIV-1 infection in monocyte-derived macrophages (MDMs), but the mechanism(s) are incompletely understood. We found that poly(I:C)- and LPS-stimulation of MDMs abrogated infection by CCR5-using, macrophage-tropic HIV-1, and by vesicular stomatitis virus glycoprotein-pseudotyped HIV-1 virions, while TLR2, TLR7 or TLR9 agonists only partially reduced infection to varying extent. Suppression of infection, or lack thereof, did not correlate with differential effects on CD4 or CCR5 expression, type I interferon induction, or production of pro-inflammatory cytokines or b-chemokines. Integrated pro-viruses were readily detected in unstimulated, TLR7- and TLR9-stimulated cells, but not in TLR3- or TLR4-stimu