Document Detail


Toll-like receptor 3 signaling inhibits simian immunodeficiency virus replication in macrophages from rhesus macaques.
MedLine Citation:
PMID:  25453343     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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:
Ming Sang; Jin-Biao Liu; Ming Dai; Jian-Guo Wu; Wen-Zhe Ho
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Publication Detail:
Type:  Journal Article     Date:  2014-10-23
Journal Detail:
Title:  Antiviral research     Volume:  112     ISSN:  1872-9096     ISO Abbreviation:  Antiviral Res.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-06     Completed Date:  -     Revised Date:  2014-12-08    
Medline Journal Info:
Nlm Unique ID:  8109699     Medline TA:  Antiviral Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  103-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
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Grant Support
ID/Acronym/Agency:
R01 DA012815/DA/NIDA NIH HHS; R01 DA022177/DA/NIDA NIH HHS; R01 DA027550/DA/NIDA NIH HHS; R21 DA036163/DA/NIDA NIH HHS

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