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-2 isolates. The collective results of this work reveal a novel molecular mechanism employed by MYH9 that helps PRRSV gain entry into permissive cells.
Highlights
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded, enveloped RNA virus belonging to the formerly designated genus Arterivirus (Nan et al, 2017)
myosin heavy chain 9 (MYH9) has been identified as the viral receptor or factor for herpes simplex virus-1 (HSV-1) (Arii et al, 2010), severe fever with thrombocytopenia syndrome virus (SFTSV) (Sun et al, 2014), Epstein-Barr virus (EBV), and PRRSV (Xiong et al, 2015; Gao et al, 2016)
To investigate whether sialic acid or N-glycosylation modification of GP5 affects the form of GP5 and GP5-MYH9 interaction, MARC-145-GP5Flag cells were treated with neuraminidase or PNGase F and lysed to conduct the investigation
Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded, enveloped RNA virus belonging to the formerly designated genus Arterivirus (Nan et al, 2017). Viral isolates from PRRSV-1 and 2 species share approximately 60% nucleotide sequence similarity and exhibit serotype differences (van Woensel et al, 1998; Forsberg, 2005). ORF1a and ORF1b account for two-thirds of the entire PRRSV genome and encode the replicase required for viral replication, while ORFs 2–7 encode most structural proteins involved in virion assembly (Lunney et al, 2016). Porcine reproductive and respiratory syndrome virus GP5 consists of approximately 200 amino acids. Based on the predicted model derived from the GP5 amino acid sequence, the GP5 protein is structurally organized into three or four predicted transmembrane domains and possesses an MYH9 Aggregation Facilitates PRRSV Internalization
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