Porcine Sapovirus Protease Controls the Innate Immune Response and Targets TBK1

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Viruses - 16(2024), 2 vom: 03. Feb.

Sprache:

Englisch

Beteiligte Personen:

Georgana, Iliana [VerfasserIn]
Hosmillo, Myra [VerfasserIn]
Jahun, Aminu S [VerfasserIn]
Emmott, Edward [VerfasserIn]
Sorgeloos, Frederic [VerfasserIn]
Cho, Kyoung-Oh [VerfasserIn]
Goodfellow, Ian G [VerfasserIn]

Links:

Volltext

Themen:

Caliciviruses
EC 2.7.11.1
EC 3.4.-
IPEC-J2
Innate immunity
Journal Article
NS6
Peptide Hydrolases
Protease
Proteasomal degradation
Protein Serine-Threonine Kinases
Sapovirus
TBK1
Type I IFN

Anmerkungen:

Date Completed 26.02.2024

Date Revised 28.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/v16020247

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368900010