The ectodomain of rabies virus glycoprotein determines dendritic cell activation.
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.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. Electronic address: junhua_huang@hotmail.com.
Junhua
J
Huang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Yachun
Y
Zhang
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Ying
Y
Huang
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Clement W
CW
Gnanadurai
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Ming
M
Zhou
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Ling
L
Zhao
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. Electronic address: zhenfu@uga.edu.
Zhen F
ZF
Fu
D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011820:Rabies virus / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D006023:Glycoproteins; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus
Dendritic cells; Glycoprotein; Rabies virus