Biyun Xue,  Gaopeng Hou,  Guixi Zhang, Jingjing Huang, Liangliang Li,  Yuchen Nan, Yang Mu, Lizhen Wang,  Lu Zhang, Ximeng Han,  Xiaolei Ren,  Qin Zhao, Chunyan Wu, Jingfei Wang and En-Min Zhou

Front Microbiol. 2019 Oct 9;10:2313. doi: 10.3389/fmicb.2019.02313. eCollection 2019.

Abstract

Prevention and control of infection by porcine reproductive and respiratory syndrome virus (PRRSV) remains a challenge, due to our limited understanding of the PRRSV invasion mechanism. Our previous study has shown that PRRSV glycoprotein GP5 interacts with MYH9 C-terminal domain protein (PRA). Here we defined that the first ectodomain of GP5 (GP5-ecto-1) directly interacted with PRA and this interaction triggered PRA and endogenous MYH9 to form filament assembly. More importantly, MYH9 filament assembly was also formed in GP5-ecto-1-transfected MARC-145 cells. Notably, PRRSV infection of MARC-145 cells and porcine alveolar macrophages also induced endogenous MYH9 aggregation and polymerization that were required for subsequent PRRSV internalization. Moreover, overexpression of S100A4, a MYH9-specific disassembly inducer, in MARC-145 cells significantly resulted in diminished MYH9 aggregation and marked inhibition of subsequent virion internalization and infection by both PRRSV-1 and PRRSV-2isolates. The collective results of this work reveal a novel molecular mechanism employed by MYH9 that helps PRRSV gain entry into permissive cells.

Copyright © 2019 Xue, Hou, Zhang, Huang, Li, Nan, Mu, Wang, Zhang, Han, Ren, Zhao, Wu, Wang and Zhou.

KEYWORDS:

GP5; MYH9; PRRSV; protein–protein interaction; virus internalization