Pathobiologie/Pathobiochemie Teil 2 - Alex Eberle

Corona-Viren
Replication of the coronaviruses occurs in the cytoplasm.
Most human coronaviruses do not grow in cultured cells, therefore
relatively little is known about them, but two strains (229E & OC43)
grow in some cell lines and have been used as a model. Replication
is slow compared to other enveloped viruses, e.g. 24 h c.f. 6-
8 h for influenza. Entry occurs via endocytosis and membrane
fusion (probably mediated by E2).
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Initially, the 5' 20kb of the (+)sense genome is translated to produce a viral polymerase, which then produces a fulllength
(-)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 and 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.
28/04/10 Pathobiologie - FS 2010 - Lektion 9 18