title: Toll-like receptor 7 ligands inhibit influenza A infection in chickens.
abstract: Avian influenza virus is endemic in many regions around the world and remains a pandemic threat, a scenario tied closely to outbreaks of the virus in poultry. The innate immune system, in particular the nucleic acid-sensing toll-like receptors (TLRs) -3, -7, -8, and -9, play a major role in coordinating antiviral immune responses. In this study we have investigated the use of TLR ligands as antivirals against influenza A in chickens. The TLR7 ligand poly-C inhibited low-path influenza A growth in the chicken macrophage cell line HD-11 more effectively than poly(I:C), which acts via TLR3. The TLR7 ligand 7-allyl-8-oxoguanosine (loxoribine) inhibited influenza A replication in vitro and in ovo in a dose-dependent manner. Treatment of primary chicken splenocytes with loxoribine resulted in the induction of interferons-α, -β, and -λ, and interferon-stimulated genes PKR and Mx. These results demonstrate that nucleic acid-sensing TLR ligands show considerable potential as antivirals in chickens and could be incorporated into antiviral strategies.
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria, Australia. cameron.stewart@csiro.au
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Stewart
authors.forename: Audrey
authors.initials: A
authors.lastname: Bagnaud-Baule
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Karpala
authors.forename: Sue
authors.initials: S
authors.lastname: Lowther
authors.forename: Peter G
authors.initials: PG
authors.lastname: Mohr
authors.forename: Terry G
authors.initials: TG
authors.lastname: Wise
authors.forename: John W
authors.initials: JW
authors.lastname: Lowenthal
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bean
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000821:virology; D004285:Dogs; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009980:Influenza A virus / Q000187:drug effects*; D005585:Influenza in Birds / Q000188:drug therapy / Q000821:virology*; D007372:Interferons / Q000378:metabolism; D008024:Ligands; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008024:Ligands; D051199:Toll-Like Receptor 7; D006151:Guanosine; D007372:Interferons; C068562:loxoribine; D011070:Poly I-C