Enterovirus A71 utilizes host cell lipid β-oxidation to promote its replication

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD), which is an infectious disease that endangers children’s health. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Metabolism and stress are known to play critical roles in multiple stages of the replication of viruses. Lipid metabolism and ER stress is an important characterization post viral infection. EV-A71 infection alters the perturbations of intracellular lipid homeostasis and induces ER stress. The characterizations induced by viral infections are essential for optimal virus replication and may be potential antiviral targets. In this study, we found that the addition of the chemical drug of ER stress, PKR IN, an inhibitor, or Tunicamycin, an activator, could significantly reduce viral replication with the decrease of lipid. The replication of viruses was reduced by Chemical reagent TOFA, an inhibitor of acetyl-CoA carboxylase (ACC) or C75, an inhibitor of fatty acid synthase (FASN), while enhanced by oleic acid (OA), which is a kind of exogenous supplement of triacylglycerol. The pharmacochemical reagent of carnitine palmitoyltransferase 1 (CPT1) called Etomoxir could knock down CPT1 to induce EV-A71 replication to decrease. This suggests that lipid, rather than ER stress, is the main factor affecting EV-A71 replication. In conclusion, this study revealed that it is the β-oxidation of lipid that plays a core role, not ER stress, which is only a concomitant change without restrictive effect, on virus replication..

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Frontiers in Microbiology - 13(2022)

Sprache:

Englisch

Beteiligte Personen:

Xiuwen Yang [VerfasserIn]
Jiayi Chen [VerfasserIn]
Zixin Lu [VerfasserIn]
Shan Huang [VerfasserIn]
Shihao Zhang [VerfasserIn]
Jintai Cai [VerfasserIn]
Yezhen Zhou [VerfasserIn]
Guanhua Cao [VerfasserIn]
Jianhai Yu [VerfasserIn]
Zhiran Qin [VerfasserIn]
Wei Zhao [VerfasserIn]
Bao Zhang [VerfasserIn]
Li Zhu [VerfasserIn]

Links:

doi.org [kostenfrei]
doaj.org [kostenfrei]
www.frontiersin.org [kostenfrei]
Journal toc [kostenfrei]

Themen:

β-Oxidition
Endoplasmic reticulum stress
Enterovirus A71
Lipid metabolism
Microbiology
Replication

doi:

10.3389/fmicb.2022.961942

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

DOAJ008911622