The role of infectious bronchitis virus accessory proteins 3a, 3b and 4b

• Main Author: Hall, Ross Howden
• Other Authors: Maier, Helena J. ; Hiscox, Julian A.
• Published: University of Liverpool 2017
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.762697

Infectious bronchitis (IB) is a respiratory disease in domestic fowl caused by the gammacoronavirus infectious bronchitis virus (IBV). Current approaches to combat this disease are hindered due to vaccines unable to cross-protect against the many different strains of IBV. To develop novel therapies or more crossprotective vaccines, a better understanding of IBV molecular biology is required. IBV is known to express four accessory proteins, 3a, 3b, 5a, and 5b, as well as a sub-genomic RNA that has the potential to code for an additional 11 kDa protein, referred to as 4b. The role of this sub-genomic RNA is not known, as is whether this transcript is translated during infection. IBV accessory proteins are dispensable for replication and are thought to play a role in virulence or pathogenicity. The functions of 3a and 3b are unknown, although they have been shown to play a part in the interferon response in a yet unknown manner. Using in vitro assays and mass spectrometry, the mechanism of action of 3a on the interferon response was determined. IBV 3a inhibits and stimulates interferon expression in a dose-dependent manner by regulating the turnover of interferon signalling proteins, MAVS and IRF7. Flow cytometry has identified a role for IBV 3b in inducing apoptosis during infection, possibly by interacting with apoptotic proteins VDAC2 or BAG6. Lastly, using an antibody raised against the predicted 4b peptide sequence, 4b was detected during infection, confirming it as the fifth IBV accessory protein. Furthermore, mass spectrometry was utilised to identify a role for 4b in regulating cellular translation and the stress granule response. Accessory proteins are highly conserved in the many different strains of IBV and are usually pathogenicity factors making them potential targets for novel therapies. Researching the role of these accessory proteins is essential to understand how IBV causes IB and for the development of more targeted therapies or more cross-protective vaccines.