Non-human coronaviruses
In other animals coronaviruses regularly infect and cause disease beyond the mucosal surfaces. In infected adult mice,for example, hepatitis is sometime a consequence of reactivation
In rats and mice, MHV stain JHM has been shown to cause demyelinating disease via an auto-immune mechanism. This is dependent on factor such as the maturity of the central nervous and immune systems. Inevitably perhaps, the coronaviruses too have been added to the list of agent, viral and otherwise, that have been implicated in the aetiology of human multiple sclerosis, none with any substantial supporting evidence.
The cause of an encephalomyelitis in pigs has been shown to be a coronavirus, haemagglutimating encephalomyelitis virus. Feline infectious peritonitis virus frequently infects populations of most species and all ages, and there is evidence for a carrier state.Although usually asymptomatic, the infection may cause severe peritonitis through antibody-dependent enhancement of infectivity and is usually fatal.
Pathogenesis
It is presumed that the major pathogenic process, at least in HCoV infection, is the direct cytolysis of infected cell as a result of viral replication. However, the ciliostasis observed in organ culture may also be a contributory factor in vivo.Since HCoV can cause disease on re-infection soon after primary infection, it cannot be excluded that humoral antibody or some other component of the immune respone has some role in causing or aggravating acute disease, but no evidence for this exists. That coronaviruses have the potential to cause disease by immunopathological mechanisms is shown in the examples already given of CNS disease in mice and rats and of peritoneal disease in cats.
Laboratory diagnosis
There is no clinical requirement for laboratory diagnosis since human respiratory tract infection with coronaviruses appear to be mild. At present, therefore, laboratory diagnosis has essentially research and epidemiological applications.
Virus isolation
Member of the OC43 group of HCoV will only grow on primary inoculation in organ culture(hence the designation).Virus growth may be detected by indirect means, such as passage to suckling mouse brain (resulting in fatal encephalitis and yielding a complement-fixing antigen from brain tissue) or by the demonstration of a haemagglutinin. Passage to diploid cell cultures may result in a cytopathic effect while infection of human volunteers may result in clinically apparent respiratory disease. Premature inhibition of ciliary motion in organ cultures, i.e. ciliostasis, can be seen. Furthermore, increasing numbers of characteristic particles due to replication can be demonstrated by electron microscopy.
In contrast to the OC43 group, the 229E group can be cultivated directly in human diploid cell such as W138 or human embryo kidney. The cytopathic effect, often described as “tatty” , resembles the non-specific degeneration of aged cultures with individual cell rounding and detaching from the cell monolayer. However, overlays such as agarose or methylcellulose may reveal the development of plaques by some strains while others produce syncytia.
Serology
Antibody to HCoV have been detected by complement fixation, by haemagglutination inhibition (some strains) and by neutralization. The last is always a complex procedure and is especially so with these viruses. More recently, reliable enyme-linked immunosorbent assay (ELISA) tests for detecting anti-HCoV antibody have been developed. ELISA is now the preferred technique although its use is still limited to research and epidemiology. Antibody is a marker of past infection but, as re-infections are well documented, such antibody cannot be regarded as reflecting immunity.