title: A novel TLR3 inhibitor encoded by African swine fever virus (ASFV).
abstract: African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes a highly glycosylated protein expressed in the cell membrane and on its surface. I329L also inhibited dsRNA-stimulated activation of NFκB and IRF3, two key players in innate immunity. Consistent with this, expression of I329L protein also inhibited the activation of interferon-β and CCL5. Finally, overexpression of TRIF reversed I329L-mediated inhibition of both NFκB and IRF3 activation. Our results suggest that TRIF, a key MyD88-independent adaptor molecule, is a possible target of this viral host modulation gene. The demonstration of an ASFV host evasion molecule inhibiting TLR responses is consistent with the ability of this virus to infect vertebrate and invertebrate hosts, both of which deploy innate immunity controlled by conserved TLR systems.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, Portugal.
authors.forename: V L
authors.initials: VL
authors.lastname: de Oliveira
authors.forename: S C P
authors.initials: SC
authors.lastname: Almeida
authors.forename: H R
authors.initials: HR
authors.lastname: Soares
authors.forename: A
authors.initials: A
authors.lastname: Crespo
authors.forename: S
authors.initials: S
authors.lastname: Marshall-Clarke
authors.forename: R M E
authors.initials: RM
authors.lastname: Parkhouse
mesh_terms: D000358:African Swine Fever Virus / Q000276:immunology* / Q000472:pathogenicity*; D000818:Animals; D002460:Cell Line; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors; D016899:Interferon-beta / Q000037:antagonists & inhibitors; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D018946:Chemokine CCL5; D006023:Glycoproteins; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; D014764:Viral Proteins; D037521:Virulence Factors; D016899:Interferon-beta