CORONAVIRIDAE

L J SAIF - Professor, MS, PhD, Food Animal Health Research Program, CFAES and CVM, OARDC/The Ohio State University, 1680 Madison Ave, Wooster, Ohio, OH 44691, USA

The families Coronaviridae and Arteriviridae with five genera (Dipartevirus, Equartevirus, Nesartevirus, Porartevirus, and Simartevirus), have been classified together in the order Nidovirales.^{1, 2}  Within the Coronaviridae, the there are two subfamilies, the Corovirinae and Torovirinae. These subfamilies contain four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus) and potentially two genera (Bafinivirus, Torovirus as well as three viruses so far unassigned to a genus), respectively.^{1, 2, 9, 14, 15}

The word ‘nidus’ is Latin for nest and refers to the fact that all viruses in this order use a unique and similar replication strategy, the so-called ‘nested set transcription’ strategy. Members of the Coronaviridae are enveloped and pleomorphic, with an overall diameter of 60-190 nm; they have a large, single-stranded, positive sense RNA genome of approximately 25.4-28 kb. The coronaviruses were so named because of the unusually large, club-shaped glycoproteins or spikes projecting from the envelope, that give the virion the appearance of a solar corona. ^{9-11, 13} The name torovirus is derived from ‘torus’ or doughnut-shape of the virions.^{6, 7}

All members of the Coronaviridae contain at least four structural proteins: a large heavily glycosylated envelope glycoprotein S (for spike), a transmembrane glycoprotein M (for membrane), a small integral membrane envelop protein and a nucleoprotein (N) that encapsulates the viral RNA.^{2, 3, 9, 11, 14} Some coronaviruses, such as bovine and some murine coronaviruses, and the bovine torovirus also have a haemagglutininesterase (HE) protein.^{3, 6, 9, 10, 14}

The Aphacoronavirus and Betacoronavirus genera are subdivided into species or subgroups (A, B, C, D, etc), and they contain viruses of pigs, cattle and horses, as well as cats, dogs, mice, rats and humans. Gammacoronaviruses contain mostly avian coronaviruses, whereas Deltacoronaviruses contain avian and a few mammalian coronaviruses (Asian leopard, cat, swine).^{2, 9, 14, 15}

The global emergence of two zoonotic coronavirus infections, the Severe Acute Respiratory Syndrome (SARS) (Betacoronavirus B) in 2003 and the unrelated Middle East Respiratory Syndrome (MERS) (Betacoronavirus C) a decade later, demonstrated the newly recognized pandemic potential of these zoonotic infections.^{9, 12, 14} Both SARS and MERS coronaviruses are suspected to have evolved from a bat-host reservoir via carnivore (civet species) or camelid (dromedary camels) intermediate hosts.^{12, 14, 5} Bats are the supposed host reservoir for these alpha and beta coronaviruses and the putative ancestral coronavirus for all mammalian coronaviruses.^{14, 15}

Although emergence of cornaviruses causing fatal pneumonia in human adults (SARS, MERS) stunned the medical community, veterinary scientists had previously established that coronaviruses cross species barriers to emerge as new strains or mutants causing severe or fatal enteric and respiratory infections in animals.^{13, 14} Coronaviruses of livestock generally cause acute infections of the respiratory or enteric tracts and transmission occurs mainly by the faecal-oral or respiratory routes.

Many of these viruses are widespread and the infections range from severe to mild or subclinical. However, infection of young piglets by several enteric coronaviruses, such as transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) is devastating due to the high morbidity (up to 100%) and mortality (up to 100%).^{8, 11, 16} High morbidity (100%) but lower mortality is also evident in neonatal pigs infected with porcine Deltacoronavirus (PDCoV).⁵   

To date, five distinct coronaviruses have been identified in pigs that consist of three Alphacoronaviruses, one Betacoronavirus, and one Deltacoronavirus.^{5, 8, 11, 14, 16} TGEV (Alphacoronavirus), first identified in diarrheic pigs in 1946, is enteric and causes severe diarrhoea and mortality in young pigs.

The association of coronaviruses with pigs is complex but can be summarised as follows:

• Porcine respiratory coronavirus (PRCV) (Alphacoronavirus), which is a deletion mutant of TGEV, was isolated in 1984. It has a major deletion in the S gene and smaller deletions or mutations in open reading frame 3 genes. Unlike TGEV, PRCV replicates in the respiratory tract and causes mostly subclinical infections. Interestingly, TGEV outbreaks have decreased in Europe after PRCV became widespread.
• PEDV (Alphacoronavirus), first isolated from diarrheic pigs in 1977, is also an enteric infection and causes severe diarrhoea and mortality in young pigs.
• Haemagglutinating encephalomyelitis virus (HEV) (betacoronavirus), isolated in 1962, is the causative agent of vomiting and wasting disease.
• PDCoV (Deltacoronavirus) identified in 2012, is also an enteric infection and causes milder diarrhoea and lower mortality in young pigs, as compared with PEDV or TGEV infection of young pigs.

In cattle and sheep, including wild ruminants, bovine coronavirus (BCV) (Betacoronavirus A) causes neonatal diarrhoea or contributes to multifactorial respiratory tract disease in calves; it is also responsible for winter dysentery in older cattle.^{10, 13, 14} In horses, equine coronavirus (ECV) (Betacoronavirus A) has occasionally been associated with...