Coronavirus Replication and Viral Maturation

The coronavirus genome consists of the longest known, sense RNA strand exceeding 30 kb, which is integrated in the envelope in the form of a helical ribonu-cleoprotein. A hallmark of coronaviral RNA replication is the production of seven subgenomic mRNAs, each of which codes for one viral structural protein. The synthesis of progeny viral RNA takes place in association with specialized membrane structures, characterized as double-membrane vesicles. Viral maturation takes place in the rough endoplasmic reticulum after replacement of cellular proteins by viral proteins in the membranes. The viruses are then transported to the Golgi apparatus. The ensuing virus release mechanism is unknown. Recently, the receptor involved in the entry of the SARS virus into the cell was reported to be the angio-tensin-converting enzyme 2 (ACE2).

Pathogenesis and clinical picture. Common cold-coronaviruses cause an everyday variety of respiratory infections, which are restricted to the ciliated epithelia of the nose and trachea. They are responsible for about 30% of common cold infections.

The immunity conferred by infection, apparently IgA-dependent, is shortlived. Reinfections are therefore frequent, whereby the antigenic variability of the virus may be a contributing factor. Various enteral coronaviruses with morphologies similar to the respiratory types have also been described in humans. Their pathogenicity, and hence their contribution to diarrhea, has not been clarified.

The SARS virus is transmitted aerogenically with an incubation time of two to 10 days. Clinically, fever and a marked shortness of breath is noted, developing into a severe atypical pneumonia with new pulmonary infiltrates on chest radiography. Shedding of virus is by respiratory discharges. Whether 8 the virus present in other body fluids and excreta plays a decisive role for virus transmission is not yet clear.

Diagnosis.The common-cold coronavirus can be grown in organ cultures of human tracheal tissue or in human diploid cells. Isolating the viruses for diagnostic purposes is not routine. Serodiagnosis (complement-binding reaction, immunofluorescence or enzyme immunoassay) and electron microscopy are feasible methods.

The SARS virus can be identified by PCR or isolated in the Vero cell line.

Epidemiology and prevention. In November 2002, an outbreak of atypical pneumonia, later termed SARS, occurred in the southern Chinese city of Guangzhou (Guangdong Province). Only in February of 2003, the world was alerted about the lung disease, shortly before it escaped China, when a Guangdong resident in a Hong Kong hotel transmitted it to other guests who spread it to Toronto, Hanoi, Singapore, and elsewhere. Transmission of the virus is by droplets, but close contact ("household transmission")

with possibly other routes of transmission seems important. The only preventive measure to date is exposure prevention. Under therapy with ribavirin and intensive care, mortality of SARS is around 10%.

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