PMID- 36918891
OWN - NLM
STAT- MEDLINE
DCOM- 20230322
LR  - 20230322
IS  - 1297-9716 (Electronic)
IS  - 0928-4249 (Print)
IS  - 0928-4249 (Linking)
VI  - 54
IP  - 1
DP  - 2023 Mar 14
TI  - Orf virus induces complete autophagy to promote viral replication via inhibition 
      of AKT/mTOR and activation of the ERK1/2/mTOR signalling pathway in OFTu cells.
PG  - 22
LID - 10.1186/s13567-023-01153-1 [doi]
LID - 22
AB  - Orf virus (ORFV) is the causative agent of contagious ecthyma, which is an 
      important zoonotic pathogen with a widespread distribution affecting sheep, goats 
      and humans. Our previous research showed that autophagy can be induced in host 
      cells by ORFV infection. However, the exact mechanism of ORFV-induced autophagy 
      remains unknown. In this study, we investigated the underlying mechanisms of 
      autophagy induced by ORFV in OFTu cells and the impact of autophagy on ORFV 
      replication. By using specific autophagy inhibitors and activators, Western 
      blotting, immunofluorescence and transmission electron microscopy imaging, we 
      confirmed that ORFV infection triggered intracellular autophagosome accumulation 
      and the activation of autophagic flux. Moreover, ORFV-induced autophagic activity 
      was found to rely on an increase in the phosphorylation of tuberous sclerosis 
      complex 2 (TSC2) and a decrease in the phosphorylation of mammalian target of 
      rapamycin (mTOR), which is mediated by the suppression of the PI3K/AKT/mTOR 
      signalling pathway and activation of the ERK1/2/mTOR signalling pathway. 
      Furthermore, we investigated the role of mTOR-mediated autophagy during ORFV 
      replication using pharmacological agents and demonstrated that ORFV-induced 
      autophagy correlated positively with viral replication. Taken together, our data 
      reveal the pathways of ORFV-induced autophagy and the impact of autophagy on ORFV 
      replication, providing new insights into ORFV pathogenesis.
CI  - (c) 2023. The Author(s).
FAU - Lv, Lijun
AU  - Lv L
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Guan, Jiyu
AU  - Guan J
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Zhen, Ruixue
AU  - Zhen R
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Lv, Pin
AU  - Lv P
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Xu, Mengshi
AU  - Xu M
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Liu, Xingyuan
AU  - Liu X
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - He, Shishi
AU  - He S
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Fang, Ziyu
AU  - Fang Z
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Li, Zi
AU  - Li Z
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Lan, Yungang
AU  - Lan Y
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Lu, Huijun
AU  - Lu H
AD  - Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin 
      University, Changchun, China.
FAU - He, Wenqi
AU  - He W
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Gao, Feng
AU  - Gao F
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
AD  - Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin 
      University, Changchun, China.
FAU - Zhao, Kui
AU  - Zhao K
AUID- ORCID: 0000-0002-4120-2050
AD  - Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China. kuizhao@jlu.edu.cn.
LA  - eng
GR  - 31672554/National Natural Science Foundation of China/
GR  - 20210202042NC/Scientific and Technological Project of Jilin Province/
GR  - 20200402052NC/Scientific and Technological Project of JiLin Province/
GR  - 419080520316/Jilin University for the Excellent Youth Scholars/
PT  - Journal Article
DEP - 20230314
PL  - England
TA  - Vet Res
JT  - Veterinary research
JID - 9309551
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Autophagy
MH  - MAP Kinase Signaling System
MH  - *Orf virus/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sheep
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Virus Replication
PMC - PMC10013242
OTO - NOTNLM
OT  - ERK1/2/mTOR
OT  - ORFV
OT  - PI3K/AKT/mTOR
OT  - autophagy
OT  - replication
COIS- The authors declare that they have no competing interests.
EDAT- 2023/03/16 06:00
MHDA- 2023/03/17 06:00
PMCR- 2023/03/14
CRDT- 2023/03/15 01:39
PHST- 2022/08/22 00:00 [received]
PHST- 2022/12/09 00:00 [accepted]
PHST- 2023/03/15 01:39 [entrez]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/17 06:00 [medline]
PHST- 2023/03/14 00:00 [pmc-release]
AID - 10.1186/s13567-023-01153-1 [pii]
AID - 1153 [pii]
AID - 10.1186/s13567-023-01153-1 [doi]
PST - epublish
SO  - Vet Res. 2023 Mar 14;54(1):22. doi: 10.1186/s13567-023-01153-1.