JGV Papers in Press. Published April 27, 2015 as doi:10.1099/vir.0.000166

Journal of General Virology Discovery of a novel nidovirus in cattle with respiratory disease --Manuscript Draft-Manuscript Number:

VIR-D-14-00290R1

Full Title:

Discovery of a novel nidovirus in cattle with respiratory disease

Short Title:

Genetic characterization of a novel nidovirus in cattle

Article Type:

Short Communication

Section/Category:

Animal - Positive-strand RNA Viruses

Corresponding Author:

Rafal Tokarz Columbia University New York, NY UNITED STATES

First Author:

Rafal Tokarz

Order of Authors:

Rafal Tokarz Stephen Sameroff Richard A. Hesse Ben M. Hause Aaloki Desai Komal Jain W. Ian Lipkin

Abstract:

The family Coronaviridae represents a diverse group of vertebrate RNA viruses, all with genomes greater than 26,000 nucleotides. Here, we report the discovery and genetic characterization of a novel virus present in cattle with respiratory disease. Phylogenetic characterization of this virus revealed that it clusters within Torovirinae, a subfamily of Coronaviridae. The complete genome consists of only 20,261 nucleotides, and represents the smallest reported Coronaviridae genome. We identified seven open reading frames, including the canonical nidovirus open reading frames 1a and b. Analysis of polyprotein 1ab revealed that this virus, tentatively named bovine nidovirus (BoNV), shares the highest homology with the recently described python-borne nidoviruses and contains several conserved nidovirus motifs, but does not encode the NendoU or O-MT domains that are present in other viruses within Coronaviridae. In concert with its reduced genome, the atypical domain architecture indicates that this virus represents a unique lineage within the order Nidovirales.

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Discovery of a novel nidovirus in cattle with respiratory disease

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Rafal Tokarz1 *, Stephen Sameroff1, Richard A. Hesse2, Ben M. Hause2, Aaloki

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Desai1, Komal Jain1, W. Ian Lipkin1

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University, NY, 10032 USA

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Medicine and Pathobiology, Kansas State University, Manhattan, KS 66508,

Center for Infection and Immunity, Mailman School of Public Health, Columbia

Kansas State Veterinary Diagnostic Laboratory and Department of Diagnostic

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USA

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* Corresponding author

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Rafal Tokarz

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Center for Infection and Immunity

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Mailman School of Public Health, Columbia University

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722 West 168th Street, Room 1701, New York, NY 10032

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phone: (212) 631 335 5021

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Email: [email protected]

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The GenBank accession number for the bovine nidovirus sequence is KM589359

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Running title: Genetic characterization of a novel nidovirus in cattle

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Contents: Animal-Positive strand viruses

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Word count

Abstract: 150

Results: 2293

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Abstract

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The family Coronaviridae represents a diverse group of vertebrate RNA viruses,

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all with genomes greater than 26,000 nucleotides. Here, we report the discovery

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and genetic characterization of a novel virus present in cattle with respiratory

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disease. Phylogenetic characterization of this virus revealed that it clusters within

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the Torovirinae, a subfamily of Coronaviridae. The complete genome consists of

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only 20,261 nucleotides, and represents the smallest reported Coronaviridae

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genome. We identified seven open reading frames, including the canonical

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nidovirus open reading frames 1a and b. Analysis of polyprotein 1ab revealed

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that this virus, tentatively named bovine nidovirus (BoNV), shares the highest

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homology with the recently described python-borne nidoviruses and contains

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several conserved nidovirus motifs, but does not encode the NendoU or O-MT

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domains that are present in other viruses within Coronaviridae. In concert with its

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reduced genome, the atypical domain architecture indicates that this virus

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represents a unique lineage within the order Nidovirales.

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Summary

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The order Nidovirales is comprised of enveloped, positive-sense, single-

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stranded RNA viruses that share similar genome organization, homology in the

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replicase polyprotein, and a unique replication strategy (deGroot et al., 2011a;

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Gorbalenya et al., 2006). The genomic architecture of nidoviruses is

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characterized by two large partially overlapping open reading frames (ORFs),

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ORF1a and ORF1b, that encode components of the viral replicase and occupy

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approximately two-thirds of the genome. ORFs encoding the structural

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components are located downstream of ORF1a/b and are expressed from 3’ co-

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terminal subgenomic mRNAs (Brian & Baric, 2005; Sawicki et al., 2007).

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Nidoviruses are taxonomically divided into four families, Arteriviridae,

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Coronaviridae, Mesoniviridae, and Roniviridae (deGroot et al., 2011a; Lauber et

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al., 2012). In addition to phylogenetic classification, genome size is a distinctive

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feature of these viral families. Arteriviruses (genome size of 12.7 kb to 15.7 kb)

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have been referred to as “small nidoviruses”, mesoniviruses (~20 kb) as

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“intermediate”, and both roniviruses (~26 kb) and coronaviruses (26-33 kb) as

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“large” (deGroot et al., 2011a; Gorbalenya et al., 2006; Nga et al., 2011). Based

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on genetic and phenotypic differences, the family Coronaviridae is further divided

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into subfamilies Coronavirinae and Torovirinae (deGroot et al., 2011b).

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Torovirinae consists of two genera, Torovirus and Bafinivirus. The Torovirus

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genus includes four viruses originating from mammals (human torovirus, bovine

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torovirus, equine torovirus, and porcine torovirus) (Beards et al., 1984; Draker et

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al., 2006; Sun et al., 2014; Weiss et al., 1983). The Bafinivirus genus includes

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two viruses isolated from fish (White Bream virus and White minnow nidovirus)

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(Batts et al., 2012; Schutze et al., 2006). Within the past year, nidoviruses have

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been described in pythons with pneumonia (Python nidovirus (PVN) and Ball

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python nidovirus (BPVN)) that are proposed to represent a novel genus within

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Torovirinae (Bodewes et al., 2014; Stenglein et al., 2014; Uccellini et al., 2014).

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Here, we report the discovery and genomic characterization of a novel virus that

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represents a distinctive lineage within this subfamily.

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In 2013, an outbreak of severe respiratory disease occurred in a cattle

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feedlot located in Southwestern United States. The animals suffered from severe

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tracheitis and pneumonia, with a high mortality rate. Although a viral agent was

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suspected, initial culture efforts were unsuccessful. In an effort to examine the

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breadth of viral agents present, post-mortem tissue samples were obtained from

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four animals and analyzed by high throughput sequencing (HTS) using the

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Illumina Hiseq 2500 platform (Table 1).

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Analysis of HTS data identified the presence of a virus with

Discovery of a novel nidovirus in cattle with respiratory disease.

The family Coronaviridae represents a diverse group of vertebrate RNA viruses, all with genomes greater than 26,000 nt. Here, we report the discovery ...
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