Ubiquitin-specific protease 18 in mallard (Anas platyrhynchos) interferes with type I interferon-mediated inhibition of high pathogenicity avian influenza virus replication

Taichiro Tanikawa; Kotaro Fujii; Yuji Sugie; Ryota Tsunekuni

doi:10.1016/j.virol.2022.10.001

Ubiquitin-specific protease 18 in mallard (Anas platyrhynchos) interferes with type I interferon-mediated inhibition of high pathogenicity avian influenza virus replication

Virology. 2022 Dec:577:32-42. doi: 10.1016/j.virol.2022.10.001. Epub 2022 Oct 9.

Authors

Taichiro Tanikawa¹, Kotaro Fujii², Yuji Sugie³, Ryota Tsunekuni⁴

Affiliations

¹ National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. Electronic address: ttanikawa@affrc.go.jp.
² Toyama Prefectural Tobu Livestock Hygiene Service Center, 46 Mizuhashi-kanao-shin, Toyama, 939-3536, Japan. Electronic address: kotaro.fujii@pref.toyama.lg.jp.
³ Shiga Prefectural Livestock Hygiene Service Center, 226-1, Nishihongou, Oumihachiman, Shiga, 523-0813, Japan. Electronic address: sugie-yuji@pref.shiga.lg.jp.
⁴ National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. Electronic address: tune@affrc.go.jp.

PMID: 36270121
DOI: 10.1016/j.virol.2022.10.001

Abstract

Ubiquitin-specific protease 18 (USP18) is a well-established innate immune factor in vertebrates. Although Anatidae birds rarely exhibit distinctive clinical signs during high pathogenicity avian influenza virus (HPAIV) infections, some virus strains cause deadly diseases. Here, we investigated the association between USP18 expression and pathogenicity during HPAIV infections in the Anatidae mallard Anas platyrhynchos. First, mallard USP18 gene (duUSP18) was cloned, and its transcriptional variants, with three different open reading frames, were characterized. Experimental infections with two different pathogenic strains, Miyazaki and Takeo, demonstrated an early induction of duUSP18 mRNA upon HPAIV infection in a bird's whole body in vivo and in primary duck cells in vitro, which was positively associated with pathogenicity in mallards. In addition, duUSP18 knockdown under interferon-β stimulation attenuated viral replication, regardless of pathogenicity. These results indicate a role for duUSP18 in favoring viral replication and virus resistance to type I interferon immunity in mallards.

Keywords: High pathogenicity avian influenza virus; Mallard; Type I interferon; Ubiquitin-specific protease 18.