The ectodomain of rabies virus glycoprotein determines dendritic cell activation

J Huang, Y Zhang, Y Huang, CW Gnanadurai, M Zhou… - Antiviral research, 2017 - Elsevier
J Huang, Y Zhang, Y Huang, CW Gnanadurai, M Zhou, L Zhao, ZF Fu
Antiviral research, 2017Elsevier
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 …
Abstract
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.
Elsevier
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