Infectious bronchitis virus (IBV)

Infectious bronchitis virus (IBV) is a gammacoronavirus in the subfamily Coronavirinae, family Coronaviridae and order Nidovirales ( IBV is endemic throughout the world and is the causative agent of an economically important poultry disease, infectious bronchitis (IB). IB is a highly contagious respiratory disease resulting in watery eyes, snicking, wheezing and rales. In addition, virus replication causes ciliostasis in the trachea. As a consequence, IB is associated with bacterial secondary infections that can lead to increased morbidity and mortality 1. IB results in poor egg quality, reduced egg production, poor meat quality and reduced weight gain. This, along with necessary disease control by vaccination, puts a large economic burden on the global poultry industry. In the UK alone, IB was estimated to cost the poultry industry £24 million per year in disease losses during the period 2000-2002 2.

Genome organisation and viral proteins

IBV has a large, single-stranded, positive sense RNA genome of approximately 27 Kb. The genome has a 5ʹ cap and a 3ʹ poly-A tail. The first two-thirds of the genome contains 2 large overlapping open reading frames, ORF 1a and ORF1b, that encode the replicase polyproteins, pp1a and pp1ab. Pp1ab is generated via a ribosomal frameshift towards the end of pp1a 3. These 2 large polyproteins are cleaved by viral proteases encoded within the polyprotein into constituent polypeptides, including the viral enzymes and other machinery required for synthesising viral RNA. Coronaviruses encode among other enzymes an RNA-dependent RNA polymerase (non-structural protein, nsp, 12), an RNA helicase (nsp13), capping machinery (nsp10, nsp14 and nsp16) and, unusually for an RNA virus, a proof-reading enzyme (nsp14) 4-6. The remaining one-third of the genome encodes four structural proteins and at least four accessory proteins 7-9. The structural and accessory proteins are translated from sub-genomic mRNAs transcribed by the viral machinery. Currently, two mRNAs are known to be polycistronic with additional open reading frames translated via leaky ribosomal scanning or via an internal ribosome entry site (IRES) 10-12.

Virus particle

The IBV particle is approximately 120 nm in diameter and has a lipid envelope. The four structural proteins assemble to generate the virus particle and three of these are glycoproteins that are inserted into the envelope. The spike (S) glycoprotein is the viral attachment and fusion protein 13. It exists as a trimer with a large head domain on the outside of the virus particle. This forms a “corona” or crown around the particle that gives coronaviruses their name. Another major component of the envelope is the membrane (M) protein, which plays a role in particle assembly 14,15. The final viral protein inserted into the envelope is the envelope (E) protein. This is a minor constituent of the envelope and plays a role during viral budding 16-18. Within the particle, the viral genome is bound by the nucleocapsid (N) protein 19,20. Other viral and cellular proteins may also be incorporated into the particle 21.

Life cycle

IBV attaches, via the S protein, to a receptor on the cell surface. Sugars are known to play a role in viral attachment to cells, although other unidentified receptor proteins may also be important 13. Following attachment, the virus particle is taken into the cell and the viral envelope fuses with the cell membrane thereby releasing the genome into the cytoplasm. As the genome has a 5′ cap and a 3′ poly-A tail, it resembles cellular mRNA and is directly translated by the ribosome. This results in expression of the viral nsps and assembly of the viral transcription machinery, the replication-transcription complex (RTC), which synthesises viral RNAs. Like the vast majority of positive sense RNA viruses, during replication IBV induces the rearrangement of cellular membranes 22. The viral RTC is thought to localise to these specialised membrane structures within the infected cell, which are termed replication organelles. This is thought to protect nascent RNA from detection by the host and provide a platform for the assembly of the large multi-component RTC. The membrane rearrangements induced by IBV include double membrane vesicles, regions of ER that become zippered together and small open-neck vesicles bound by two membranes that remain tethered to the zippered ER, called spherules 23,24.

Viral RNA is synthesised via a negative sense intermediate in a discontinuous manner (reviewed in 25). The transcription machinery proceeds along the template RNA until it reaches the genomic transcription regulatory sequence (TRS) located at the 5′ end of each ORF. Here, the transcription machinery either reads through the TRS and continues transcribing along the genome until the next TRS or detaches and reattaches at a complementary sequence called the leader TRS near the 5′ end of the genome. Once reattached, the transcription machinery continues until the end of the template. This generates the 3′ co-terminal nested set of RNAs. Positive sense viral mRNAs are then synthesised by the transcription machinery from these sub-genomic negative sense copies.

Following RNA synthesis, viral structural and accessory proteins are translated and new viral particles assemble. The envelope glycoproteins are inserted into the ER and trafficked to the ER-Golgi intermediate compartment and this is where new particles form. Viral budding occurs in a process that requires interactions between S, M, E and N 15,17,18,26-28. Finally, enveloped particles are released from the cell via exocytosis. Progeny virions begin to be released from cells in culture by 6 hours post infection and progeny continues to be released until the cell dies 23.


The virus initially infects the respiratory tract. Following infection here, some strains of IBV are able to spread to secondary sites of infection including the oviducts and the kidneys. Virus replication in the oviducts affects egg production with fewer eggs being laid and an increase in poor quality or shell-less eggs. In addition, some more recent highly pathogenic strains of IBV result in severe damage to the oviducts and generation of “false-layers” or birds with large numbers of abdominal cysts creating a distended abdomen and a “penguin-like stance” 29.


Several vaccines are available for prevention of IBV. There are both inactivated vaccines and live-attenuated vaccines. Live-attenuated vaccines are produced by serial passage in embryonated eggs to reduce pathogenicity in adult birds. However, there is a delicate balance between reducing pathogenicity and maintaining immunogenicity. The molecular basis of attenuation in these vaccine strains is not understood and will likely be different in each new vaccine produced. Despite the number of available vaccines, IBV continues to cause new outbreaks. This is due to the very large number of different strains and poor-cross protection between different strains ( In addition, new viral strains emerge on a regular basis due to the relatively high mutation rate of the genome and recombination between co-circulating IBV strains 30-33. Development of novel ways to produce vaccines is a major area of research in the field.


Contributed by: Helena Maier (The Pirbright Institute)

Copyright © 2016 Helena Maier

First posted: 16-Sept-2016


1               Vandekerchove, D., Herdt, P. D., Laevens, H., Butaye, P., Meulemans, G. & Pasmans, F. (2004) Significance of interactions between Escherichia coli and respiratory pathogens in layer hen flocks suffering from colibacillosis-associated mortality. Avian Pathology 33, 298-302, doi:10.1080/030794504200020399.

2               Reading, U. o. Economic assessment of livestock diseases in Great Britain, 2002).

3               Brierley, I., Boursnell, M. E., Binns, M. M., Bilimoria, B., Blok, V. C., Brown, T. D. & Inglis, S. C. (1987) An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV. The EMBO Journal 6, 3779-3785.

4               Ziebuhr, J. (2006) The coronavirus replicase: insights into a sophisticated enzyme machinery. Adv Exp Med Biol 581, 3-11, doi:10.1007/978-0-387-33012-9_1.

5               Chen, Y. & Guo, D. (2016) Molecular mechanisms of coronavirus RNA capping and methylation. Virologica Sinica 31, 3-11, doi:10.1007/s12250-016-3726-4.

6               Denison, M. R., Graham, R. L., Donaldson, E. F., Eckerle, L. D. & Baric, R. S. (2011) Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity. RNA Biology 8, 270-279, doi:10.4161/rna.8.2.15013.

7               Bentley, K., Keep, S. M., Armesto, M. & Britton, P. (2013) Identification of a Noncanonically Transcribed Subgenomic mRNA of Infectious Bronchitis Virus and Other Gammacoronaviruses. Journal of Virology 87, 2128-2136, doi:10.1128/jvi.02967-12.

8               Casais, R., Davies, M., Cavanagh, D. & Britton, P. (2005) Gene 5 of the Avian Coronavirus Infectious Bronchitis Virus Is Not Essential for Replication. Journal of Virology 79, 8065-8078, doi:10.1128/jvi.79.13.8065-8078.2005.

9               Hodgson, T., Britton, P. & Cavanagh, D. (2006) Neither the RNA nor the Proteins of Open Reading Frames 3a and 3b of the Coronavirus Infectious Bronchitis Virus Are Essential for Replication. Journal of Virology 80, 296-305, doi:10.1128/jvi.80.1.296-305.2006.

10            Liu, D. X., Cavanagh, D., Green, P. & Inglis, S. C. (1991) A polycistronic mRNA specified by the coronavirus infectious bronchitis virus. Virology 184, 531-544.

11            Liu, D. X. & Inglis, S. C. (1992) Internal entry of ribosomes on a tricistronic mRNA encoded by infectious bronchitis virus. Journal of Virology 66, 6143-6154.

12            Liu, D. X. & Inglis, S. C. (1992) Identification of two new polypeptides encoded by mRNA5 of the coronavirus infectious bronchitis virus. Virology 186, 342-347.

13            Wickramasinghe, I. N. A., van Beurden, S. J., Weerts, E. A. W. S. & Verheije, M. H. (2014) The avian coronavirus spike protein. Virus Research 194, 37-48, doi:

14            Wang, J., Fang, S., Xiao, H., Chen, B., Tam, J. P. & Liu, D. X. (2009) Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding. PLoS ONE 4, e4908, doi:10.1371/journal.pone.0004908.

15            Narayanan, K., Maeda, A., Maeda, J. & Makino, S. (2000) Characterization of the Coronavirus M Protein and Nucleocapsid Interaction in Infected Cells. Journal of Virology 74, 8127-8134, doi:10.1128/jvi.74.17.8127-8134.2000.

16            Liu, D. X. & Inglis, S. C. (1991) Association of the infectious bronchitis virus 3c protein with the virion envelope. Virology 185, 911-917, doi:

17            Machamer, C. E. & Youn, S. in The Nidoviruses: Toward Control of SARS and other Nidovirus Diseases   (eds Stanley Perlman & Kathryn V. Holmes) 193-198 (Springer US, 2006).

18            Ruch, T. R. & Machamer, C. E. (2011) The Hydrophobic Domain of Infectious Bronchitis Virus E Protein Alters the Host Secretory Pathway and Is Important for Release of Infectious Virus. Journal of Virology 85, 675-685, doi:10.1128/jvi.01570-10.

19            Baric, R. S., Nelson, G. W., Fleming, J. O., Deans, R. J., Keck, J. G., Casteel, N. & Stohlman, S. A. (1988) Interactions between coronavirus nucleocapsid protein and viral RNAs: implications for viral transcription. Journal of Virology 62, 4280-4287.

20            Zhou, M. & Collisson, E. W. (2000) The amino and carboxyl domains of the infectious bronchitis virus nucleocapsid protein interact with 3′ genomic RNA. Virus Research 67, 31-39, doi:

21            Dent, S. D., Xia, D., Wastling, J. M., Neuman, B. W., Britton, P. & Maier, H. J. (2015) The proteome of the infectious bronchitis virus Beau-R virion. J Gen Virol 96, 3499-3506.

22            Romero-Brey, I. & Bartenschlager, R. (2014) Membranous replication factories induced by plus-strand RNA viruses. Viruses 6, 2826-2857, doi:10.3390/v6072826.

23            Maier, H. J., Hawes, P. C., Cottam, E. M., Mantell, J., Verkade, P., Monaghan, P., Wileman, T. & Britton, P. (2013) Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes. MBio 4, e00801-00813, doi:10.1128/mBio.00801-13.

24            Maier, H. J., Neuman, B. W., Bickerton, E., Keep, S. M., Alrashedi, H., Hall, R. & Britton, P. (2016) Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity. Sci Rep 6, 27126, doi:10.1038/srep27126.

25            Sawicki, S. G., Sawicki, D. L. & Siddell, S. G. (2007) A Contemporary View of Coronavirus Transcription. Journal of Virology 81, 20-29, doi:10.1128/jvi.01358-06.

26            Corse, E. & Machamer, C. E. (2000) Infectious Bronchitis Virus E Protein Is Targeted to the Golgi Complex and Directs Release of Virus-Like Particles. Journal of Virology 74, 4319-4326, doi:10.1128/jvi.74.9.4319-4326.2000.

27            Corse, E. & Machamer, C. E. (2003) The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction. Virology 312, 25-34, doi:

28            Lontok, E., Corse, E. & Machamer, C. E. (2004) Intracellular Targeting Signals Contribute to Localization of Coronavirus Spike Proteins near the Virus Assembly Site. Journal of Virology 78, 5913-5922, doi:10.1128/jvi.78.11.5913-5922.2004.

29            Landman, W., RM;, D. & JJ, d. W. in Fifty-fourth Western Poultry Disease Conference.

30            Cavanagh, D., Davis, P., Cook, J. & Li, D. (1990) Molecular basis of the variation exhibited by avian infectious bronchitis coronavirus (IBV). Adv Exp Med Biol 276, 369-372.

31            Cavanagh, D., Davis, P. J. & Cook, J. K. A. (1992) Infectious bronchitis virus: Evidence for recombination within the Massachusetts serotype. Avian Pathology 21, 401-408, doi:10.1080/03079459208418858.

32            Kottier, S. A., Cavanagh, D. & Britton, P. (1995) First experimental evidence of recombination in infectious bronchitis virus. Recombination in IBV. Adv Exp Med Biol 380, 551-556.

33            Jackwood, M. W., Hall, D. & Handel, A. (2012) Molecular evolution and emergence of avian gammacoronaviruses. Infection, Genetics and Evolution 12, 1305-1311, doi: