Hypoxia inducible factor-1α facilitates transmissible gastroenteritis virus replication by inhibiting type I and type III interferon production

Copyright © 2024 Elsevier B.V. All rights reserved..

Transmissible gastroenteritis virus (TGEV) is characterized by watery diarrhea, vomiting, and dehydration and is associated with high mortality especially in newborn piglets, causing significant economic losses to the global pig industry. Hypoxia inducible factor-1α (HIF-1α) has been identified as a key regulator of TGEV-induced inflammation, but understanding of the effect of HIF-1α on TGEV infection remains limited. This study found that TGEV infection was associated with a marked increase in HIF-1α expression in ST cells and an intestinal organoid epithelial monolayer. Furthermore, HIF-1α was shown to facilitate TGEV infection by targeting viral replication, which was achieved by restraining type I and type III interferon (IFN) production. In vivo experiments in piglets demonstrated that the HIF-1α inhibitor BAY87-2243 significantly reduced HIF-1α expression and inhibited TGEV replication and pathogenesis by activating IFN production. In summary, we unveiled that HIF-1α facilitates TGEV replication by restraining type I and type III IFN production in vitro, ex vivo, and in vivo. The findings from this study suggest that HIF-1α could be a novel antiviral target and candidate drug against TGEV infection.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:292

Enthalten in:

Veterinary microbiology - 292(2024) vom: 30. Apr., Seite 110055

Sprache:

Englisch

Beteiligte Personen:

Zhang, Yunhang [VerfasserIn]
Rui, Xue [VerfasserIn]
Li, Yang [VerfasserIn]
Zhang, Yue [VerfasserIn]
Cai, Yifei [VerfasserIn]
Tan, Chen [VerfasserIn]
Yang, Ning [VerfasserIn]
Liu, Yuanyuan [VerfasserIn]
Fu, Yuguang [VerfasserIn]
Liu, Guangliang [VerfasserIn]

Links:

Volltext

Themen:

HIF-1α
In vivo
Interferon Lambda
Intestinal organoid monolayer
Journal Article
TGEV
Type I and type III IFN production

Anmerkungen:

Date Completed 10.04.2024

Date Revised 10.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.vetmic.2024.110055

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370031024