title: Toll-like receptor 3 signaling inhibits simian immunodeficiency virus replication in macrophages from rhesus macaques.
abstract: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA and induces multiple intracellular events responsible for innate antiviral immunity against viral infections. Here we demonstrate that TLR3 signaling of monocyte-derived macrophages (MDM) from rhesus monkeys by poly I:C inhibited simian immunodeficiency virus (SIV) infection and replication. Investigation of the mechanisms showed that TLR3 activation resulted in the induction of type I and type III interferons (IFNs) and IFN-inducible antiviral factors, including APOBEC3G (A3G), tetherin and SAMHD1. In addition, poly I:C-treated macaque macrophages expressed increased levels of CC chemokines including CCL3, CCL4 and CCL5, the ligands for HIV or SIV coreceptor CCR5. Furthermore, TLR3 signaling of macaque macrophages induced the expression of cellular microRNAs (miR-29a, -29b, -146a and -9), the newly identified intracellular SIV restriction factors. TLR3 activation-mediated anti-SIV effect could be compromised by the knockdown of IRF3 and IRF7. These findings indicate that TLR3-mediated induction of multiple viral restriction factors contribute to the inhibition of SIV infection in macaque macrophages, which support future preclinical studies using rhesus macaques to determine whether in vivo TLR3 activation is safe and beneficial for treating people infected with HIV.
authors.affiliation: ABSL-III Laboratory at the Center for Animal Experiment, Wuhan University School of Basic Medical Sciences, Wuhan, People's Republic of China; State Key Laboratory of Virology, Wuhan University, Wuhan, People's Republic of China; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, College of Basic Medical Sciences, Hubei University of Medicine, Shiyan, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sang
authors.affiliation: ABSL-III Laboratory at the Center for Animal Experiment, Wuhan University School of Basic Medical Sciences, Wuhan, People's Republic of China; State Key Laboratory of Virology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jin-Biao
authors.initials: JB
authors.lastname: Liu
authors.affiliation: ABSL-III Laboratory at the Center for Animal Experiment, Wuhan University School of Basic Medical Sciences, Wuhan, People's Republic of China; Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wu
authors.affiliation: ABSL-III Laboratory at the Center for Animal Experiment, Wuhan University School of Basic Medical Sciences, Wuhan, People's Republic of China; State Key Laboratory of Virology, Wuhan University, Wuhan, People's Republic of China; Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, United States. Electronic address: wenzheho@temple.edu.
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008253:Macaca mulatta; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D011070:Poly I-C / Q000378:metabolism; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D051196:Toll-Like Receptor 3; D011070:Poly I-C
keywords: CC chemokine; Interferon; Rhesus macaques; Simian immunodeficiency virus (SIV); Toll-like receptor 3 (TLR3); microRNA