Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production

Binbin Ding, Guangyuan Zhang, Xiaodan Yang, Shengwei Zhang, Longyun Chen, Qin Yan, Mengyao Xu, Amiya K. Banerjee, and Mingzhou Chen.

Cell Host & Microbe 15, 564–577, 2014.

Speaker: Yu-Rou Liao (廖毓柔)                                    Time: 14:00~15:00, Oct 22, 2014

Commentator: Dr. Hsiao-Sheng Liu (劉校生 老師)   Place: Room 601

Abstract:

Autophagy is a cellular degradation process that maintains homeostasis and defends against microbial infection. Some viruses have developed strategies to avoid or subvert autophagy for their own benefit. In the present study, the authors focused on the importance of autophagy in the replication of human parainfluenza virus type 3 (HPIV3), one of the major causes of respiratory disease in children. They revealed that HPIV3 infection induced autophagosome formation and inhibited autophagosome-lysosome fusion, resulting in autophagosome accumulation in cells. The accumulated autophagosomes enhanced extracellular viral yields, but failed to affect viral protein synthesis and intracellular viral yields. These results show that autophagosome accumulation promotes HPIV3 release. To study the mechanism by which HPIV3 induces incomplete autophagy, cells were transiently transfected with viral proteins, and the expression of phosphoprotein (P) significantly induced autophagosome accumulation. Furthermore, the authors revealed that P interacted with the SNARE domain of synaptosomal-associated protein 29 (SNAP29), which has been shown to promote autophagosome-lysosome fusion via interacting with SNARE domains of syntaxin 17 on autophagosomal membrane and VAMP8 on lysosomal membrane¹. Cells with HPIV3 infection or P expression alone disrupted the interaction of SNAP29 and syntaxin 17. Furthermore, knock-down of SNAP29 expression in HPIV3-infected cells further accumulatedautophagosomes and increased virus release. Collectively, these evidences show that P interacts with SNAP29 via SNARE domain to block autophagosome-lysosome fusion for HPIV3 release. This is the first study showing that virus inhibits autophagosome-lysosome fusion by blocking the interaction of SNARE proteins.

Reference:

1          Itakura, E., Kishi-Itakura, C. & Mizushima, N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151, 1256-1269, 2012.