Chapter 60 Coronaviruses

Tyrrell DAJ, Myint SH.

General Concepts

Clinical Presentation
Coronaviruses cause acute, mild upper respiratory infection (common cold).

Structure
Spherical or pleomorphic enveloped particles containing single-stranded (positive-sense) RNA associated with a nucleoprotein
within a capsid comprised of matrix protein. The envelope bears club-shaped glycoprotein projections.

Classi cation
Coronaviruses (and toroviruses) are classified together on the basis of the crown or halo-like appearance of the envelope
glycoproteins, and on characteristic features of chemistry and replication. Most human coronaviruses fall into one of two
serotypes: OC43-like and 229E-like.

Multiplication
The virus enters the host cell, and the uncoated genome is transcribed and translated. The mRNAs form a unique “nested set”
sharing a common 3′ end. New virions form by budding from host cell membranes.

Pathogenesis
Transmission is usually via airborne droplets to the nasal mucosa. Virus replicates locally in cells of the ciliated epithelium,
causing cell damage and inflammation.

Host Defenses
The appearance of antibody in serum and nasal secretions is followed by resolution of the infection. Immunity wanes within a
year or two.

Epidemiology
Incidence peaks in the winter, taking the form of local epidemics lasting a few weeks or months. The same serotype may
return to an area after several years.

Diagnosis
Colds caused by coronaviruses cannot be distinguished clinically from other colds in any one individual. Laboratory diagnosis
may be made on the basis of antibody titers in paired sera. The virus is difficult to isolate. Nucleic acid hybridization tests
(including PCR) are now being introduced.

Control
Treatment of common colds is symptomatic; no vaccines or specific drugs are available. Hygiene measures reduce the rate of
transmission.

Introduction
Coronaviruses are found in avian and mammalian species. They resemble each other in morphology and chemical structure:
for example, the coronaviruses of humans and cattle are antigenically related. There is no evidence, however, that human
coronaviruses can be transmitted by animals. In animals, various coronaviruses invade many different tissues and cause a
variety of diseases, but in humans they are only proved to cause mild upper respiratory infections, i.e. common colds. On rare
occasions, gastrointestinal coronavirus infection has been associated with outbreaks of diarrhoea in children, but these
enteric viruses are not well characterized and are not discussed in this chapter.

Clinical Manifestations
Coronaviruses invade the respiratory tract via the nose. After an incubation period of about 3 days, they cause the symptoms
of a common cold, including nasal obstruction, sneezing, runny nose, and occasionally cough (Figs. 60-1 and 60-2). The disease
resolves in a few days, during which virus is shed in nasal secretions. There is some evidence that the respiratory
coronaviruses can cause disease of the lower airways but it is unlikely that this is due to direct invasion. Other manifestations
of disease such as multiple sclerosis have been attributed to these viruses but the evidence is not clear-cut.

Figure 60-1
Clinical manifestations and pathogenesis of coronavirus infections.

Figure 60-2
Immunopathogenesis of coronavirus infections.

Structure
Coronavirus virions are spherical to pleomorphic enveloped particles (Fig. 60-3). The envelope is studded with projecting
glycoproteins, and surrounds a core consisting of matrix protein enclosed within which is a single strand of positive-sense
RNA (Mr 6 × 106) associated with nucleoprotein. The envelope glycoproteins are responsible for attachment to the host cell and
also carry the main antigenic epitopes, particularly the epitopes recognized by neutralizing antibodies. OC43 also possesses a
haemagglutin.

Figure 60-3
Electron micrograph showing human coronavirus 229E. Bar, 100 mn (Courtesy S.Sikotra, Leicester Royal
Infirmary, Leicester, England.)

Classi cation and Antigenic Types

The coronaviruses were originally grouped into the family Coronaviridae on the basis of the crown or halo-like appearance
given by the glycoprotein-studded envelope on electron microscopy. This classification has since been confirmed by unique
features of the chemistry and replication of these viruses. Most human coronaviruses fall into one of two groups: 229E-like and
OC43-like. These differ in both antigenic determinants and culturing requirements: 229E-like coronaviruses can usually be
isolated in human embryonic fibroblast cultures; OC43-like viruses can be isolated, or adapted to growth, in suckling mouse
brain. There is little antigenic cross-reaction between these two types. They cause independent epidemics of indistinguishable
disease.

Multiplication
It is thought that human coronaviruses enter cells, predominantly, by specific receptors. Aminopeptidase-N and a sialic acid-
containing receptor have been identified to act in such a role for 229E and OC43 respectively. After the virus enters the host
cell and uncoats, the genome is transcribed and then translated. A unique feature of replication is that all the mRNAs form a
“nested set” with common 3′ ends; only the unique portions of the 5′ ends are translated. There are 7 mRNAs produced. The
shortest mRNA codes for the nucleoprotein, and the others each direct the synthesis of a further segment of the genome. The
proteins are assembled at the cell membrane and genomic RNA is incorporated as the mature particle forms by budding from
internal cell membranes.

Pathogenesis
Studies in both organ cultures and human volunteers show that coronaviruses are extremely fastidious and grow only in
differentiated respiratory epithelial cells. Infected cells become vacuolated, show damaged cilia, and may form syncytia. Cell
damage triggers the production of inflammatory mediators, which increase nasal secretion and cause local inflammation and
swelling. These responses in turn stimulate sneezing, obstruct the airway, and raise the temperature of the mucosa.

Host Defenses
Although mucociliary activity is designed to clear the airways of particulate material, coronaviruses can successfully infect the
superficial cells of the ciliated epithelium. Only about one-third to one-half of infected individuals develop symptoms,
however. Interferon can protect against infection, but its importance is not known. Because coronavirus infections are
common, many individuals have specific antibodies in their nasal secretions, and these antibodies can protect against
infection. Most of these antibodies are directed against the surface projections and neutralize the infectivity of the virus. Cell-
mediated immunity and allergy have been little studied, but may play a role.

Figure 60-4
Seasonal incidence of coronavirus infections.

Epidemiology
The epidemiology of coronavirus colds has been little studied. Waves of infection pass through communities during the winter
months, and often cause small outbreaks in families, schools, etc. (Fig. 60-2). Immunity does not persist, and subjects may be
re-infected, sometimes within a year. The pattern thus differs from that of rhinovirus infections, which peak in the fall and
spring and generally elicit long-lasting immunity. About one in five colds is due to coronaviruses.

The rate of transmission of coronavirus infections has not been studied in detail. The virus is usually transmitted via
inhalation of contaminated droplets, but it may also be transmitted by the hands to the mucosa of the nose or eyes.

Diagnosis
There is no reliable clinical method to distinguish coronavirus colds from colds caused by rhinoviruses or less common agents.
For research purposes, virus can be cultured from nasal swabs or washings by inoculating organ cultures of human fetal or
nasal tracheal epithelium. The virus in these cultures is detected by electron microscopy or other methods. The most useful
method for laboratory diagnosis is to collect paired sera (from the acute and convalescent phases of the disease) and to test by
ELISA for a rise in antibodies against OC43 and 229E. Complement fixation tests are insensitive; other tests are inconvenient
and can be used only for one serotype. Direct hybridization and polymerase chain reaction tests for viral nucleic acid have
been developed and, particularly with the latter, are the most sensitive assays currently available for detecting virus .

Control
Although antiviral therapy has been attempted, the treatment of coronavirus colds remains symptomatic. The likelihood of
transmission can be reduced by practising hygienic measures. Vaccines are not currently available.

References
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coronaviruses 229E and OC43 in clinical specimens. Mol Cell Probes. 1994;8:357–364. [PubMed: 7877631]
 3. Sanchez CM, Jimenez G, Laviada MD. et al. Antigenic homology among coronaviruses related to transmissible
gastroenteritis virus. Virology. 1990;174:410. [PubMed: 1689525]
4. Schmidt OW, Allan ID, Cooney MK. et al. Rises in titers of antibody to human coronaviruses OC43 and 229E in Seattle
families during 1975–1979. Am J Epidemiol. 1986;123:862. [PubMed: 3008551]
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[PubMed: 3058868]
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Publication Details

Author Information

Authors

David A.J. Tyrrell and Steven H. Myint.

Copyright
Copyright © 1996, The University of Texas Medical Branch at Galveston.

Publisher

University of Texas Medical Branch at Galveston, Galveston (TX)

NLM Citation

Tyrrell DAJ, Myint SH. Coronaviruses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter
60.