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Interspecies protein substitution to investigate the role of the lyssavirus glycoprotein
- Source :
- The Journal of General Virology
- Publication Year :
- 2013
- Publisher :
- Microbiology Society, 2013.
-
Abstract
- European bat lyssaviruses type 1 (EBLV-1) and type 2 (EBLV-2) circulate within bat populations throughout Europe and are capable of causing disease indistinguishable from that caused by classical rabies virus (RABV). However, the determinants of viral fitness and pathogenicity are poorly understood. Full-length genome clones based on the highly attenuated, non-neuroinvasive, RABV vaccine strain (SAD-B19) were constructed with the glycoprotein (G) of either SAD-B19 (SN), of EBLV-1 (SN-1) or EBLV-2 (SN-2). In vitro characterization of SN-1 and SN-2 in comparison to wild-type EBLVs demonstrated that the substitution of G affected the final virus titre and antigenicity. In vivo, following peripheral infection with a high viral dose (104 f.f.u.), animals infected with SN-1 had reduced survivorship relative to infection with SN, resulting in survivorship similar to animals infected with EBLV-1. The histopathological changes and antigen distribution observed for SN-1 were more representative of those observed with SN than with EBLV-1. EBLV-2 was unable to achieve a titre equivalent to that of the other viruses. Therefore, a reduced-dose experiment (103 f.f.u.) was undertaken in vivo to compare EBLV-2 and SN-2, which resulted in 100 % survivorship for all recombinant viruses (SN, SN-1 and SN-2) while clinical disease developed in mice infected with the EBLVs. These data indicate that interspecies replacement of G has an effect on virus titre in vitro, probably as a result of suboptimal G–matrix protein interactions, and influences the survival outcome following a peripheral challenge with a high virus titre in mice.
- Subjects :
- RNA viruses
Antigenicity
Virulence Factors
Biology
medicine.disease_cause
Virus
Mice
Viral Proteins
Antigen
In vivo
Rhabdoviridae Infections
Virology
medicine
Animals
Antigens, Viral
Lyssavirus
Glycoproteins
Recombination, Genetic
Histocytochemistry
Animal
Rabies virus
Brain
Viral Load
biology.organism_classification
Immunohistochemistry
Survival Analysis
Recombinant Proteins
Standard
Disease Models, Animal
Titer
Viral load
Subjects
Details
- ISSN :
- 14652099 and 00221317
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Journal of General Virology
- Accession number :
- edsair.doi.dedup.....9427568e41f71c5b95c9a8477ff923f1