Chapter 23 : Coronaviruses and Arteriviruses

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This chapter summarizes the interactions of coronaviruses and arteriviruses with the innate immune response, including the type I interferon (IFN) system; and the strategies employed by these viruses to evade or inhibit the antiviral IFN response. Coronaviruses and arteriviruses are a group of enveloped animal RNA viruses that are united in the order . Very little is known about the inhibition of the type I IFN pathway by arteriviruses, while significant advances have been made, primarily using MHV and SARS-CoV, toward understanding how coronaviruses evade type I IFN induction and the type I IFN signaling pathway. Devaraj et al. showed that the papain-like protease (PLpro) domain of the SARS-CoV replicase protein, nsp3, one of the gene 1 proteins, is an IFN antagonist. In this report, using a plasmid-based expression system, the authors showed that PLpro interacts with IRF3 and inhibits its phosphorylation and nuclear translocation, thereby affecting the downstream activation of the type I IFN gene. Some studies have shown that coronaviruses employ posttranscriptional strategies to suppression general host gene expression in infected cells. The availability of transgenic and other valuable natural mouse models for MHV, SARS-CoV, and HCoV-229E enables researchers to investigate the role of nonstructural and accessory proteins in virulence and pathogenesis. Using such systems, the potential identification of some common, evolutionarily conserved molecular mechanisms of immune evasion among different groups of coronaviruses is an exciting possibility in the future.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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Figure 1

Simplified scheme of the type I IFN activation and signaling pathways and their inhibition by coronaviruses. Internalization of RNA viruses exposes the genomic RNA to cytoplasmic RNA sensors like RIG-I, MDA-5, and LGP2 that recognize dsRNA and 5′-triphosphate ssRNA produced during the life cycle of RNA viruses. In the endosomes, RNA sensors like TLR3 and TLR7/8 recognize dsRNA and ssRNA, respectively. TLR3 and TLR7/8 signal through the adaptor proteins TRIF and MyD88, respectively, to activate IFN-α/β production. RIG-I and MDA-5 trigger signaling cascades via IPS-1, an adaptor protein on mitochondrial membrane, to activate IRF3, leading to IFN-β gene expression and production of IFN-β protein. The released IFN-α/β proteins bind to the cognate type I IFN receptors in the same cell or neighboring cells to activate a Stat-dependent pathway to trigger the induction of ISGs with ISRE promoter sequences. The different steps in the IFN activation and signaling pathways that are inhibited or targeted by coronaviral proteins, as discussed in the text, are indicated. IKK, Ikappa B kinase; IRAK, IL-1 receptor-associated; TBK, TANK (TRAF family member-associated NF-κB activator)-binding kinase; TRAF, tumor necrosis factor (TNF) receptor-associated factor.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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Figure 2

Genome organization of selected members in the and families. The replicase ORFs, ORF1a and ORF1b, and the names of the major virion structural genes are indicated. The accessory genes are shown as black boxes. The figure is not drawn to scale. EAV, equine arteritis virus; RFS, ribosomal frameshift.

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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Figure 3

Schematic representation of the nidovirus life cycle. Virus entry is triggered by attachment to the cellular receptor and fusion of the viral envelope to the plasma membrane or the endosomes, which releases the viral genome into the cytoplasm. The genome is translated to produce precursor polyproteins, pp1a and pp1ab, which are proteolytically processed to produce mature viral proteins necessary for replication and transcription. The replication machinery, localized on DMVs, produces the viral genomic RNA, minus-strand RNAs, and subgenomic mRNAs. Viral mRNAs are translated to produce proteins that undergo modifications in cellular compartments like ER/Golgi. Viral assembly and budding occurs on an ER/Golgi intermediate compartment (ERGIC), where the viral envelope proteins and viral RNPs are assembled into virus particles. The mature virus particles are exported in vesicles to the cell surface and released into the extracellular environment by fusion with the cell membrane. (Adapted from Fig. 6 in reference .)

Citation: Narayanan K, Makino S. 2009. Coronaviruses and Arteriviruses, p 373-387. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch23
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