title: Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines.
abstract: Different rabies virus (RABV) strains have their own biological characteristics, but little is known about their respective impact on autophagy. Therefore, we evaluated whether attenuated RABV HEP-Flury and wild-type RABV GD-SH-01 strains triggered autophagy. We found that GD-SH-01 infection significantly increased the number of autophagy-like vesicles, the accumulation of enhanced green fluorescent protein (EGFP)-LC3 fluorescence puncta and the conversion of LC3-I to LC3-II, while HEP-Flury was not able to induce this phenomenon. When evaluating autophagic flux, we found that GD-SH-01 infection triggers a complete autophagic response in the human neuroblastoma cell line (SK), while autophagosome fusion with lysosomes was inhibited in a mouse neuroblastoma cell line (NA). In these cells, GD-SH-01 led to apoptosis and mitochondrial dysfunction while triggering autophagy, and apoptosis could be decreased by enhancing autophagy. To further identify the virus constituent causing autophagy, 5 chimeric recombinant viruses carrying single genes of HEP-Flury instead of those of GD-SH-01 were rescued. While the HEP-Flury virus carrying the wild-type matrix protein (M) gene of RABV triggered LC3-I to LC3-II conversion in SK and NA cells, replacement of genes of nucleoprotein (N), phosphoprotein (P) and glycoprotein (G) produced only minor autophagy. But no one single structural protein of GD-SH-01 induced autophagy. Moreover, the AMPK signaling pathway was activated by GD-SH-01 in SK. Therefore, our data provide strong evidence that autophagy is induced by GD-SH-01 and can decrease apoptosis in vitro. Furthermore, the M gene of GD-SH-01 may cooperatively induce autophagy.
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Peng
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Shenghe
authors.initials: S
authors.lastname: Zhu
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Hu
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Ye
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tian
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Mei
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: a College of Veterinary Medicine , South China Agricultural University , Guangzhou , China.|b Key Laboratory of Zoonosis Prevention and Control of Guangdong Province , Guangzhou , China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D000071182:Autophagosomes / Q000378:metabolism / Q000648:ultrastructure; D001343:Autophagy; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000473:pathology; D009447:Neuroblastoma / Q000473:pathology* / Q000648:ultrastructure / Q000821:virology*; D011818:Rabies / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D000263:Adenylate Kinase
keywords: apoptosis; autophagic flux; autophagosome; autophagy; matrix protein; rabies virus