The ectodomain of rabies virus glycoprotein determines dendritic cell activation

• Published in: Antiviral research 2017-05, Vol.141, p.1-6
• Main Authors: Huang, Junhua, Zhang, Yachun, Huang, Ying, Gnanadurai, Clement W., Zhou, Ming, Zhao, Ling, Fu, Zhen F.
• Format: Article
• Language: English
• Subjects: Antigens, Viral - chemistry; Antigens, Viral - immunology; Antigens, Viral - metabolism; Cell Differentiation; Cells, Cultured; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - virology; Glycoprotein; Glycoproteins - chemistry; Glycoproteins - immunology; Glycoproteins - metabolism; Protein Sorting Signals - genetics; Protein Structure, Tertiary - genetics; Rabies virus; Rabies virus - chemistry; Rabies virus - genetics; Rabies virus - growth & development; Rabies virus - immunology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.01.022

The immune evasion of wild-type (wt) rabies virus (RABV) has been attributed to its glycoprotein (G), particularly to their inefficiency to bind/enter into dendritic cells (DCs). However, the domain responsible for G-mediated DC activation is not clear. In the present study, attempts were made to map the domain(s) on the G involved in differential DC activation using laboratory-adapted and wt viruses. Recombinant RABVs with exchange in each of the structural domains such as signal peptide (sp), ectodomain (et), transmembrane domain (tm), cytoplasmic tail (ct) of the G between wt and laboratory-adapted strains were constructed. Characterizations of these recombinant RABVs show that the viruses containing the sp, tm and ct from the wt G are capable of growing in high titer by efficient cell-to-cell spread, similar to laboratory-adapted virus. On the other hand, recombinant virus containing the et domain from wt G was inefficient in cell-to-cell spread and grew in lower levels, similar to the wt RABV. Analysis of DC activation shows that viruses containing sp and tm from wt G are efficient in binding to and activating DCs. However, viruses containing the et domain from wt G are incompetent in binding to and activating DCs. Analysis of the G expression in the infected cells suggests that the level of G expression is regulated solely by the ct domain, indicating the level of G expression and DC activation are governed by different domains. Together, our results demonstrate that G-mediated DC activation is regulated by the et domain while the level of G expression by the ct domain. •Recombinant RABVs containing the ectodomain of SHBRV G was inefficient in cell to cell spreading and grew in lower levels.•DC activation is mainly regulated by the ectodomain of G protein.•The level of G protein expression is regulated solely by the cytoplasmic tail.