Phosphoprotein of human parainfluenza virus type 3 blocks autophagosome-lysosome fusion to increase virus production.
Autophagy is a multistep process in which cytoplasmic components, including invading pathogens, are captured by autophagosomes that subsequently fuse with degradative lysosomes. Negative-strand RNA viruses, including paramyxoviruses, have been shown to alter autophagy, but the molecular mechanisms remain largely unknown. We demonstrate that human parainfluenza virus type 3 (HPIV3) induces incomplete autophagy by blocking autophagosome-lysosome fusion, resulting in increased virus production. The viral phosphoprotein (P) is necessary and sufficient to inhibition autophagosome degradation. P binds to SNAP29 and inhibits its interaction with syntaxin17, thereby preventing these two host SNARE proteins from mediating autophagosome-lysome fusion. Incomplete autophagy and resultant autophagosome accumulation increase extracellular viral production but do not affect viral protein synthesis. These findings highlight how viruses can block autophagosome degradation by disrupting the function of SNARE proteins.
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Binbin
B
Ding
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Guangyuan
G
Zhang
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Xiaodan
X
Yang
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Shengwei
S
Zhang
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Longyun
L
Chen
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Qin
Q
Yan
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China.
Mengyao
M
Xu
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Amiya K
AK
Banerjee
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, People's Republic of China. Electronic address: chenmz@whu.edu.cn.
Mingzhou
M
Chen
D001343:Autophagy; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D008561:Membrane Fusion; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000502:physiology*; D010588:Phagosomes / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D010253:Respirovirus Infections / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D010750:Phosphoproteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; D014764:Viral Proteins