First isolated from chickens in 1937. After the discovery of Rhinoviruses in the 1950's, >50% of colds still could not be ascribed to known agents.
Introduction:
First isolated from chickens in 1937. After the discovery of
Rhinoviruses in the 1950's, >50% of colds still could not be ascribed to known agents. In 1965, Tyrrell and Bynoe used cultures of human cilliated embryonal trachea to propagate the first human Coronavirus in vitro.
There are now ~13 species in this Family, which infect not only man but cattle, pigs, rodents, cats, dogs and birds (some are serious veterinary pathogens, especially chickens).
Morphology:
Particles are irregularly-shaped, ~60-220nm in diameter, with an outer envelope bearing distinctive, 'club-shaped' peplomers (~20nm long x 10nm at wide distal end). This 'crown-like' appearance gives the family its name. Centre of particle appears amorphous in -ve stained EM preps, the nucleocapsid being in a loosely wound rather disordered state.
The envelope carries two glycoproteins:
The genome is associated with a basic phosphoprotein, N.
Genome:
Non-segmented, s/s, (+)sense RNA, 27-31 kb (dependent on virus) - the longest of any RNA virus. Genome has 5' methylated cap and 3' poly-A and functions directly as mRNA (unlike (-)sense RNA viruses, no polymerase in particles!) - but this is a bit more complex than at first sight (below).
Replication:
Generally, human Corona's do not grow in cultured cells, therefore relatively little is known about them, but 2 strains (229E & OC43) grow in some cell lines & have been used as a model. Replication is slow compared to other enveloped viruses, e.g. 24h c.f. 6-8h for influenza.
Entry occurs via endocytosis & membrane fusion (probably mediated by E2). Replication occurs in the cytoplasm.
Initially, the 5' 20kb of the (+)sense genome is translated to produce a viral polymerase, which then produces a full-length (-)sense strand (this step is poorly understood). This is used as a template to produce mRNA as a 'nested set' of transcripts, all with an identical 5' non-translated leader sequence of 72nt & coincident 3' polyadenylated ends:
Each mRNA is monocistronic, the genes at the 5' end being translated from the longest mRNA & so on. These unusual cytoplasmic structures are produced not by splicing (post-transcriptional modification) but by the polymerase during transcription. Between each of the genes there is a repeated intergenic sequence - UCUAAAC - which interacts with the transcriptase plus cellular factors to 'splice' the leader sequence onto the start of each ORF.
Assembly occurs by budding into the golgi apparatus, particles being transported to the surface of the cell by the secretory nature of this organelle & released.
Pathogenesis:
These viruses infect a variety of mammals & birds. The exact number of human isolates are not known as many cannot be grown in culture. They cause:
- respiratory infections (common)
- enteric infections (occasional - mostly in infants >12 mo.)
- neurological syndromes (???)
Transmitted by aerosols of respiratory secretions, growth appears to be localized in epithelium of U.R.T. but there is no adequate animal model for the human respiratory coronaviruses. Clinically, most infections cause a mild, self-limited disease (classical 'cold' or upset stomach), but there may be rare neurological complications. Greatest incidence in children in winter, less common in adults. Number of serotypes/extent of antigenic variation unknown. Re-infections appear to occur throughout life (implying multiple serotypes (at least 4 are known) and/or antigenic variation) hence prospects for immunization appear bleak.
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