Changes in nonstructural protein 3 are associated with attenuation in avian coronavirus infectious bronchitis virus

Phillips, Jamie E.; Jackwood, Mark W.; McKinley, Enid T.; Thor, Sharmi; Hilt, Deborah A.; Acevedol, N. D.; Williams, Susan M.; Kissinger, Jessica C.; Paterson, Andrew H.; Robertson, Jon S.; Lemke, Cornelia

doi:10.1007/s11262-011-0668-7

Cited by 31 publications

(27 citation statements)

References 42 publications

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“…Positions were based on 1ab from IBV Beaudette strain (accession number NC_001451), and modified according to Ziebuhr (2005), with position 1 the methionine at the beginning of ORF 1a and 1ab. b Based on Phillips et al (2012). The mutations in nsp6 of VicS-del (Table 1) may have implications for the replication of this virus, which would be consistent with data from previous in vivo studies (Hewson et al, 2012).…”

Section: Discussionsupporting

confidence: 81%

“…The ORFs 4b and 4c have been described in IBV (Hewson et al, 2011(Hewson et al, , 2012Thor et al, 2011;Phillips et al, 2012;Bentley et al, 2013), as well as in TCoV (Cao et al, 2008), and have been synthesized in vitro (Bentley et al, 2013), but the products of these ORFs are yet to be identified in infected cells, and their function remains unknown. Both these ORFs could be identified in the VicS-v genome, but in VicS-del, 4b was divided into two smaller ORFs due to a singlenucleotide deletion.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of the complete genomic sequences of two virus subpopulations of the Australian infectious bronchitis virus vaccine VicS

et al. 2015

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Although sequencing of the 3′ end of the genome of Australian infectious bronchitis viruses (IBVs) has shown that their structural genes are distinct from those of IBVs found in other countries, their replicase genes have not been analysed. To examine this, the complete genomic sequences of the two subpopulations of the VicS vaccine, VicS-v and VicS-del, were determined. Compared with VicS-v, the more attenuated VicS-del strain had two nonsynonymous changes in the non-structural protein 6 (nsp6), a transmembrane (TM) domain that may participate in autocatalytic release of the 3-chymotrypsin-like protease, a polymorphic difference at the end of the S2 gene, which coincided with the body transcription-regulating sequence (B-TRS) of mRNA 3 and a truncated open reading frame for a peptide encoded by gene 4 (4b). These genetic differences could be responsible for the differences between these variants in pathogenicity in vivo, and replication in vitro. Phylogenetic analysis of the whole genome showed that VicS-v and VicS-del did not cluster with strains from other countries, supporting the hypothesis that Australian IBV strains have been evolving independently for some time, and analyses of individual polymerase peptide and S glycoprotein genes suggested a distant common ancestor with no recent recombination. This study suggests the potential role of the TM domain in nsp6, the integrity of the S2 protein and the B-TRS 3, and the putative accessory protein 4b, as well as the 3′ untranslated region, in the virulence and replication of IBV and has provided a better understanding of relationships between the Australian vaccine strain of IBV and those used elsewhere.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Analysis of the complete genomic sequences of two virus subpopulations of the Australian infectious bronchitis virus vaccine VicS

et al. 2015

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“…The predominance of KM91-like 1ab genes supports the hypothesis that they conferred more favorable biological properties to the recombinants than the QX-like 1ab genes. For example, they may have conferred efficient virus replication and extended persistence in the trachea [34]. Based on the nucleotide and amino acid sequence identities, nsp 2, 3, 4, 5, and 6 were more variable than the other nsps among the viruses (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Comparative genomics of QX-like infectious bronchitis viruses in Korea

et al. 2017

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To minimize the spread of infectious bronchitis virus (IBV), domestic fowl have been extensively vaccinated with the KM91 strain. However, various IBV QX-like virus strains have become increasingly prevalent in Korea. We conducted comparative genomic analyses of seven QX-like viruses: early viruses (n = 2), new cluster 1 (NC1; recombinants of KM91 and the early QX-like viruses, n = 3) and recurrent viruses (n = 2), to understand their genomic backgrounds. The early and NC1 viruses had KM91-like backgrounds, but the recurrent viruses had QX-like genomic backgrounds. The absence of pure QX-like viruses before the appearance of the early viruses suggests that the viruses were introduced from other countries after recombination, but the NC1 viruses originated in Korea. The recent prevalence of recurrent viruses with different genomic backgrounds and spike genes from the early and the NC1 viruses may indicate the repeated introduction of different infectious bronchitis viruses from other countries and their successful evasion of vaccine immunity in the field. Furthermore, a 1ab gene-based phylogenetic analysis revealed three distinct lineages: North America-Europe, China/Taiwan, and China. KM91 and the early and NC1 viruses were included in the North America-Europe lineage, and the recurrent QX-like viruses were included in the China lineage. The phylogenetic positions of KM91-like 1ab and QX-like spike suggest frequent recombination between the North America-Europe and China lineages. Additional studies on the patterns of recombination, including donor-acceptor relationships, geographical sites, and non-poultry hosts, may be valuable for understanding the evolution of IBVs.

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“…Most notably, ArkGA P60 had SNPs in the nsp2, nsp3, and both S1 and S2 gene regions. Changes in nsp2 and nsp3, which are part of the viral replicase complex, have been shown to impact viral replication and pathogenesis [32][33][34][35][36][37][38]. In the spike gene, which is the major determinant of cell tropism and plays a role in viral attenuation [39,40], 5 amino acid changes occurred in the S1 and S2 subunits.…”

Section: Discussionmentioning

confidence: 99%

Biological and molecular characterization of ArkGA: A novel Arkansas serotype vaccine that is highly attenuated, efficacious, and protective against homologous challenge

Albanese

Lee

Cheng

et al. 2018

Vaccine

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Almost all commercial poultry are vaccinated against avian coronavirus infectious bronchitis virus (IBV) using live attenuated vaccines mass administered by spray at day of hatch. Although many different types of IBV vaccines are used successfully, the ArkDPI serotype vaccine, when applied by spray, does not infect and replicate sufficiently to provide protection against homologous challenge. In this study, we examined a different Ark vaccine strain (Ark99), which is no longer used commercially due to its reactivity in one day old chicks, to determine if it could be further attenuated by passage in embryonated eggs but still provide adequate protection. Further attenuation of the Ark99 vaccine was achieved by passage in embryonated eggs but ArkGA P1, P20, and P40 (designated ArkGA after P1) were still too reactive to be suitable vaccine candidates. However, ArkGA P60 when given by spray had little or no vaccine reaction in one day old broiler chicks, and it induced protection from clinical signs and ciliostasis following homologous challenge. In addition, vaccinated and challenged birds had significantly less challenge virus, an important measure of protection, compared to non-vaccinated and challenged controls. The full-length genomes of viruses from egg passages 1, 20, 40, and 60 were sequenced using the Illumina platform and the data showed single nucleotide polymorphisms (SNPs) had accumulated in regions of the genome associated with viral replication, pathogenicity, and cell tropism. ArkGA P60 accumulated the most SNPs in key genes associated with pathogenicity (polyprotein gene 1ab) and cell tropism (spike gene), compared to previous passages, which likely resulted in its more attenuated phenotype. These results indicate that the ArkGA P60 vaccine is safe for spray vaccination of broiler chicks and induces suitable protection against challenge with pathogenic Ark-type virus.

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Changes in nonstructural protein 3 are associated with attenuation in avian coronavirus infectious bronchitis virus

Cited by 31 publications

References 42 publications

Analysis of the complete genomic sequences of two virus subpopulations of the Australian infectious bronchitis virus vaccine VicS

Analysis of the complete genomic sequences of two virus subpopulations of the Australian infectious bronchitis virus vaccine VicS

Comparative genomics of QX-like infectious bronchitis viruses in Korea

Biological and molecular characterization of ArkGA: A novel Arkansas serotype vaccine that is highly attenuated, efficacious, and protective against homologous challenge

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