Porcine Sapovirus Protease Controls the Innate Immune Response and Targets TBK1.

Georgana, Iliana, Hosmillo, Myra, Jahun, Aminu S, Emmott, Edward ORCID: 0000-0002-3239-8178, Sorgeloos, Frederic, Cho, Kyoung-Oh and Goodfellow, Ian G (2024) Porcine Sapovirus Protease Controls the Innate Immune Response and Targets TBK1. Viruses, 16 (2). p. 247.

Access the full-text of this item by clicking on the Open Access link.

Official URL: http://dx.doi.org/10.3390/v16020247

Abstract

Human sapoviruses (HuSaVs) and noroviruses are considered the leading cause of acute gastroenteritis worldwide. While extensive research has focused on noroviruses, our understanding of sapoviruses (SaVs) and their interactions with the host's immune response remains limited. HuSaVs have been challenging to propagate in vitro, making the porcine sapovirus (PSaV) Cowden strain a valuable model for studying SaV pathogenesis. In this study we show, for the first time, that PSaV Cowden strain has mechanisms to evade the host's innate immune response. The virus 3C-like protease (NS6) inhibits type I IFN production by targeting TBK1. Catalytically active NS6, both during ectopic expression and during PSaV infection, targets TBK1 which is then led for rapid degradation by the proteasome. Moreover, deletion of TBK1 from porcine cells led to an increase in PSaV titres, emphasizing its role in regulating PSaV infection. Additionally, we successfully established PSaV infection in IPEC-J2 cells, an enterocytic cell line originating from the jejunum of a neonatal piglet. Overall, this study provides novel insights into PSaV evasion strategies, opening the way for future investigations into SaV-host interactions, and enabling the use of a new cell line model for PSaV research.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Animals, Swine, Sapovirus, Caliciviridae Infections, Peptide Hydrolases, Gene Expression, Immunity, Innate, Protein Serine-Threonine Kinases
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	06 Mar 2024 10:57
Last Modified:	06 Mar 2024 10:57
DOI:	10.3390/v16020247
Open Access URL:	https://doi.org/10.3390/v16020247
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179185