Infectious bronchitis coronavirus limits interferon production by inducing a host shutoff that requires accessory protein 5b

During infection of their host cell, viruses often inhibit production of host proteins, a process which is referred to as host shutoff. By doing this, viruses limit production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the Alpha- and Betacoronavirus genera, such as severe acute respiratory syndrome coronavirus (SARS-CoV) establish host shutoff via their non-structural protein 1 (nsp1). The genomes of Gamma- and Deltacoronaviruses however do not encode nsp1, and it has been suggested that these viruses do not induce host shutoff. Here we show that infectious bronchitis Gammacoronavirus (IBV) does induce host shutoff and we find that its accessory protein 5b is indispensable for this function. Importantly, we found that 5b-null viruses, unlike wild type viruses, induce production of high concentrations of type I interferon protein in vitro, indicating that host shutoff by IBV plays an important role in antagonizing the host's innate immune response. Altogether we demonstrate that 5b is a functional equivalent of nsp1 thereby answering the long-standing question whether lack of nsp1 in Gammacoronaviruses is compensated for by another viral protein. As such, our study is a significant step forward in the understanding of coronavirus biology and closes a gap in the understanding of some IBV virulence strategies.IMPORTANCE Many viruses inhibit protein synthesis of their host cell to enhance virus replication and antagonize anti-viral defense mechanisms. This process is referred to as ‘host-shutoff'. We have studied gene expression and protein synthesis in chicken cells infected with the important poultry pathogen, infectious bronchitis virus (IBV). We show that IBV inhibits synthesis of host proteins, including that of type I interferon, a key component of the antiviral response. The IBV-induced host shutoff however, does not require degradation of host RNA. Furthermore, we demonstrate that accessory protein 5b of IBV plays a crucial role in the onset of the host shutoff. Our findings suggest that inhibition of host protein synthesis is a common feature of coronaviruses and primarily serves to inhibit the antiviral response of the host.