Temperature Sensitivity: A Potential Method for the Generation of Vaccines against the Avian Coronavirus Infectious Bronchitis Virus
Open Access
- 14 July 2020
- Vol. 12 (7), 754
- https://doi.org/10.3390/v12070754
Abstract
The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious economically important respiratory pathogen of domestic fowl. Reverse genetics allows for the molecular study of pathogenic determinants to enable rational vaccine design. The recombinant IBV (rIBV) Beau-R, a molecular clone of the apathogenic Beaudette strain, has previously been investigated as a vaccine platform. To determine tissues in which Beau-R could effectively deliver antigenic genes, an in vivo study in chickens, the natural host, was used to compare the pattern of viral dissemination of Beau-R to the pathogenic strain M41-CK. Replication of Beau-R was found to be restricted to soft tissue within the beak, whereas M41-CK was detected in beak tissue, trachea and eyelid up to seven days post infection. In vitro assays further identified that, unlike M41-CK, Beau-R could not replicate at 41 °C, the core body temperature of a chicken, but is able to replicate a 37 °C, a temperature relatable to the very upper respiratory tract. Using a panel of rIBVs with defined mutations in the structural and accessory genes, viral replication at permissive and non-permissive temperatures was investigated, identifying that the Beau-R replicase gene was a determinant of temperature sensitivity and that sub-genomic mRNA synthesis had been affected. The identification of temperature sensitive allelic lesions within the Beau-R replicase gene opens up the possibility of using this method of attenuation in other IBV strains for future vaccine development as well as a method to investigate the functions of the IBV replicase proteins.Keywords
Funding Information
- Biotechnology and Biological Sciences Research Council (BB/M012794/1, BB/M012069/1, BBS/E/I/00007031, BBS/E/I/00007034, BBS/E/I/00007038)
This publication has 73 references indexed in Scilit:
- Infectious Bronchitis Virus Generates Spherules from Zippered Endoplasmic Reticulum MembranesmBio, 2013
- A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal diseaseNature Medicine, 2012
- Temperature-Sensitive Mutants and Revertants in the Coronavirus Nonstructural Protein 5 Protease (3CLpro) Define Residues Involved in Long-Distance Communication and Regulation of Protease ActivityJournal of Virology, 2012
- A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 SerotypePLOS ONE, 2011
- The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of PathogenicityPLOS ONE, 2009
- Mouse Hepatitis Virus Liver Pathology Is Dependent on ADP-Ribose-1″-Phosphatase, a Viral Function Conserved in the Alpha-Like SupergroupJournal of Virology, 2008
- The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunitJournal of General Virology, 2008
- A Novel Mutation in Murine Hepatitis Virus nsp5, the Viral 3C-Like Proteinase, Causes Temperature-Sensitive Defects in Viral Growth and Protein ProcessingJournal of Virology, 2008
- Mutation in murine coronavirus replication protein nsp4 alters assembly of double membrane vesiclesVirology, 2008
- Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase ProteinsPLoS Pathogens, 2005