PMID- 33566740 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20220311 IS - 1557-8976 (Electronic) IS - 0882-8245 (Linking) VI - 34 IP - 4 DP - 2021 May TI - The Role of Autophagy in Murine Cytomegalovirus Hepatitis. PG - 241-255 LID - 10.1089/vim.2020.0024 [doi] AB - Autophagy is involved in the pathogenesis of multiple pathogen infection. Previous studies have reported that human cytomegalovirus (CMV) activates autophagy in the early stage of infection and then inhibits autophagy. Little is known about the role of autophagy in murine CMV (MCMV) infection, especially in MCMV-induced hepatitis. The purpose of this study is to investigate the role of autophagy in MCMV hepatitis. BALB/c mice were infected with MCMV and a series of experiments involving western blot, immunofluorescence, immunohistochemistry, H&E (Hematoxylin and Eosin) staining and quantitative real-time polymerase chain reaction were performed in this study. The expression of SQSTM1/p62, PI3K, the ratio of phosphorylated Akt to total Akt, and the ratio of phosphorylated mammalian target of rapamycin (mTOR) to total mTOR were increased, and the expression of light-chain 3 (LC3)-II were decreased in the livers of infected mice on days 3 and 7 postinfection (p.i.). Compared with the untreated infected group, increased transcription level of MCMV glycoprotein B (gB), increased expression levels of interleukin1-beta (IL-1beta), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), decreased expression level of type I interferon alpha (IFN-alpha), as well as aggravated liver pathological injury were detected in starvation-treated infected group on days 3 and 7 p.i.; whereas decreased transcription level of MCMV gB, decreased expression levels of IL-1beta, AST and ALT, increased expression level of type I IFN-alpha, as well as alleviated liver pathological injury were detected in chloroquine (CQ)-treated infected group on day 3 p.i. In conclusion, autophagy is inhibited through activating the PI3K/Akt/mTOR pathway in the liver of BALB/c mice during MCMV infection, and autophagy may promote MCMV replication and aggravate liver pathological damage and inflammation. Further understanding of the interactions between autophagy and MCMV infection and its potential mechanism may bring new important cues to the control of MCMV infection and antiviral therapy. FAU - Zhang, Lin-Lin AU - Zhang LL AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Xin-Yan AU - Zhang XY AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Lu, Yuan-Yuan AU - Lu YY AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Bi, Yi-Dan AU - Bi YD AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Xing-Lou AU - Liu XL AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Fang, Feng AU - Fang F AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210209 PL - United States TA - Viral Immunol JT - Viral immunology JID - 8801552 SB - IM MH - Animals MH - Autophagy MH - Cytomegalovirus/physiology MH - *Cytomegalovirus Infections/complications MH - *Hepatitis MH - Mice MH - Mice, Inbred BALB C MH - *Muromegalovirus MH - Phosphatidylinositol 3-Kinases/metabolism OTO - NOTNLM OT - LC3-II OT - autophagy OT - hepatitis OT - murine cytomegalovirus OT - p62 EDAT- 2021/02/11 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/02/10 17:11 PHST- 2021/02/11 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/02/10 17:11 [entrez] AID - 10.1089/vim.2020.0024 [doi] PST - ppublish SO - Viral Immunol. 2021 May;34(4):241-255. doi: 10.1089/vim.2020.0024. Epub 2021 Feb 9.