Deficient Incorporation of Rabies Virus Glycoprotein into Virions Enhances Virus-Induced Immune Evasion and Viral Pathogenicity

• Main Authors: Chunfu Li, Hongliang Zhang, Lina Ji, Xiao Wang, Yongjun Wen, Guangpeng Li, Zhen F. Fu, Yang Yang
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: Viruses
• Subjects: rabies virus; immune evasion; glycoprotein incorporation; laboratory-attenuated rabies virus; wild-type rabies virus; dendritic cell activation; membrane fusion
• Online Access: http://www.mdpi.com/1999-4915/11/3/218

Previous studies have shown that wild-type (wt) rabies virus (RABV) evades the host immune response by restricting expression of glycoprotein (G), which blocks activation of dendritic cells (DCs) and induces production of virus-neutralizing antibodies (VNAs). In the present study, wt RABVs not only restricted G expression but also reduced incorporation of G into mature virions compared with laboratory-adapted viruses. A recombinant RABV expressing triple G was used to further determine whether G expression relates to incorporation. The recombinant virus showed higher expression and incorporation of G and activated more DCs than the virus that expressed a single copy of G. Removal of G from viruses using subtilisin or Dithiothreitol (DTT)/ Nonidet P-40 (NP40) almost completely abolishes DC activation and VNA production. Consequently, these G-depleted viruses cause lethal infection in mice. Thus, wt RABVs can subvert DC-induced antiviral immune response and maintain pathogenicity by decreasing G expression in infected cells and G incorporation into virions.