10 Coronaviruses and Toroviruses David Cavanagh Institute for Animal Health, Newbury, UK INTRODUCTION Human coronaviruses (HCVs) are usually thought of in the context of the common cold and, indeed, these viruses are responsible for up to one-third of colds. There is also evidence for coronaviruses be- ing associated with enteric disease in humans. HCVs can grow in some neural cells in vitro and have been associated with cases of multiple scler- osis, although the role of the coronavirus in such cases is not clear. The alimentary tract is certainly a site of replication of toroviruses, including those of humans; these viruses superfi cially resemble co- ronaviruses, with which they may be confused. Coronaviruses were fi rst isolated in humans in themid-1960s(TyrrellandBynoe,1965;Hamreand Procknow, 1966). The original coronavirus strains were passaged in organ cultures of human embry- onic trachea or nasal epithelium and in primary human kidney cell cultures. Subsequently several other HCVs have been isolated in organ or tissue cultures. The majority of HCVs studied to date are serologically related to one of two reference strains, 229EandOC43.Molecularanalysishasshownthat these two viruses diff er extensively from each other; they are distinct species of coronavirus, not simply variants of each other. Toroviruses were fi rst isolated from diarrhoeic horse in 1972 (Berne virus, BEV) and neonatal calves 1982 (bovine torovirus, BoTV, strain Breda virus, BRV) (Weiss and Horzinek, 1987). Subse- quently particles resembling these two viruses were observed by electron microscopy in the stools of children and adults with diarrhoea (Beards et al., 1984). The human viruses formed immunocom- plexes with anti-BEV and BoTV sera. Much less is known about human toroviruses than corona- viruses. THE VIRUSES The coronaviruses, in the single genus Coronavirus, were for many years the only members of the family Coronaviridae. Recently the genus Torovirus was included in this family. Moreover, certain charac- teristics relating to genome organization, transcrip- tion and translation resulted in the creation of the order Nidovirales comprising the families Co- ronaviridae and Arteriviridae (Cavanagh, 1997; de Vries et al., 1997). No arteriviruses, which are mor- phologicallydistinctfromcoronavirusesand toroviruses, have yet been discovered in humans. Both coronaviruses and toroviruses comprise RNA-containing viruses of similar size and gross appearance. The coronaviruses are largely asso- ciated with respiratory and enteric infections in mammals and birds, while to date the fewer known toroviruses have been associated with diarrhoea (Dales and Anderson, 1995; Koopmans and Hor- zinek, 1995; Myint, 1995; Siddell, 1995a; Lai and Cavanagh, 1997). The large surface projections of the coronaviruses gave them an appearance remi- niscent of a crown, hence the name coronaviruses (Latin corona, crown; Figures 10.1 and 10.2). The doughnut shape sometimes seen within torovirus Principles and Practice of Clinical Virology, Fourth Edition. Edited by A. J. Zuckerman, J. E. Banatvala and J. R. Pattison. 2000 John Wiley 0-470-84247-4 (Electronic) Copyright 2000 John Wiley Houtman and Fleming, 1996). Porcine hae- magglutinating encephalomyelitis virus (HEV) also selectively infect neuronal tissue. Coronaviruses have been assigned to one of groups 1, 2 and 3 (Table 10.1) on the basis of amino acid sequences, supported to some extent by antigenic analyses. Structure Coronaviruses are pleomorphic, ether-labile, envel- oped viruses with diameters ranging from 60 to 220nm and have a buoyant density in sucrose of 1.151.18ml?(as dotoroviruses).Theparticles are often described as having club-shaped surface pro- jections or spikes (S) of up to 20nm in length, al- though the shape varies among the species. Par- ticles may be seen with incomplete coronas of spikes. Toroviruses are 100140nm in diameter and are variously described as being doughnut-, disc-, kid- ney- or rod-shaped, dependingon the angle of view. The large spikes of BEV and BoTV measure ap- proximately 1720nm in length and are not unlike those of some coronaviruses in appearance (Weiss et al., 1983). However, many particles of BEV, which had been prepared for electron microscopy were devoid of the 20nm S protein, the virions having a smooth surface (Weiss et al., 1983). Simi- larly, electronmicroscopyof BoTV has revealed few of the 20nm spikes but rather an intact fringe of smallerspikes,some 79nm inlength (Woodeet al., 1982; Cornelissen et al., 1997). The toroviruses re- cently isolated from human faeces had an intact fringe of 10nm spikes (Duckmanton et al., 1997), which resembled those seen on human toroviruses by Beards and colleagues (Beards et al., 1984). The latter reported observing the 20nm spikes only rarely. It is possible that the 10nm spikes observed by Duckmanton and colleagues are haemagglu- tinin-esterase (HE) protein. It has recently been shownthatBoTV,incontrasttoBEV(whic