Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1-mediated autophagy signaling pathway
- PDF / 4,065,311 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 36 Downloads / 207 Views
(2020) 18:153
RESEARCH
Open Access
Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1mediated autophagy signaling pathway Juan Liu1, Min Liao1*, Yan Yan1, Hui Yang1, Hailong Wang1 and Jiyong Zhou1,2
Abstract Background: Rabies virus (RABV) is reported to encode five phosphoproteins (P), which are involved in viral genomic replication, axonal transport, oxidative stress, interferon antagonism, and autophagy induction. However, the functions of the different P proteins are poorly understood. Methods: Immunofluorescence staining and western blot were performed to detect the autophagy activity, the form of ring-like structure, and the colocalization of BECN1 and P. Co-immunoprecipitation was performed to detect the interaction between P and BECN1. QRT-PCR and TCID50 assay were performed to detect the replication level of RABV. Small interfering RNA was used to detect the autophagy signaling pathway. Results: We found that P5 attaches to N-terminal residues 1–139 of BECN1 (beclin1) on the BECN1 ring-like structure through amino acid residues 173–222 of P5. Subsequently, we found that P5-induced autophagosomes did not fuse with lysosomes. Becn1 silencing did not recover P5 overexpression-induced promotion of RABV replication. Mechanistically, RABV protein PΔN82 (P5) induced incomplete autophagy via the BECN1-mediated signaling pathway. Conclusions: Our data indicate that P5 binding to the BECN1 ring benefits RABV replication by inducing BECN1 signaling pathway-dependent incomplete autophagy, which provides a potential target for antiviral drugs against RABV. Keywords: Rabies virus phosphoprotein P5, Beclin1, Binding domain, Incomplete autophagy, Viral replication
Background Rabies is associated with severe neurological symptoms and a high mortality rate, causing over 59,000 human deaths worldwide each year [1]. Rabies virus (RABV), belonging to the Rhabdoviridae family, is a single nonsegmented negative-stranded RNA virus with genome of 12 kb. The RABV genome encodes a nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA polymerase (L) [2]. The RABV M protein * Correspondence: [email protected] 1 MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China Full list of author information is available at the end of the article
induces apoptosis by targeting mitochondria [3]. The viral protein P is a multifunctional protein that is involved in viral transcription and replication [4]. The P protein–dynein LC8 interaction is involved in the axonal transport of rabies virus along microtubules through neuronal cells [5]. The interaction of RABV P protein with complex I in mitochondria causes mitochondrial dysfunction, increased generation of reactive oxygen species (ROS), and oxidative stress [6]. In addition, the interaction of RABV P protein with the focal adhesion kinase and nucleolin positively regulates viral replication [7]. However, RABV P protein also direct
Data Loading...
