Coronaviridae

Coronaviruses are enveloped, single stranded, positive-sense RNA viruses (27-31kb) with club-shaped surface about 120-160 nm in diameter that resemble a “corona”. Both 5' and 3' ends of the genome have a cap and poly (A) tract respectively. The envelope consists of two viral-specified structural glycoproteins S and M. Glycoprotein S is located on the outer membrane of the envelope and is responsible for the club-shaped projections. On the other hand, glycoprotein M is a transmembrane molecule and is located on the inner part of the envelope. Another important structural protein is the phosphoprotein N which is responsible for the helical symmetry of the nucleocapsid that encloses the genomic RNA.

The Coronaviridae are a family of viruses, including the following genera:

• Genus Coronavirus; type species: Infectious bronchitis virus
• Genus Torovirus; type species: Equine torovirus

Transmission

Coronaviruses are transmitted by faecal-oral route or by aerosols of respiratory secretions.

Pathogenesis

Coronaviruses infect a wide range of mammals and birds and occur worldwide. Although most diseases are mild, sometimes they can cause more severe situations in humans, such as for example the infection of the respiratory tract known as Severe Acute Respiratory Syndrome (SARS). They can also cause enteric infections in very young infants and in rare situations neurological syndromes.

SARS

Human infection by SARS coronavirus appears to be limited to the respiratory tract where infection of susceptible cells leads to damage to the pneumocytes resulting in a histological picture of diffuse alveolar damage and a clinical picture of adult respiratory distress syndrome. Diarrhea is also present but there is limited evidence of damage to the intestinal epithelium. The damage to the respiratory tree appears limited to the lower respiratory tract and there is evidence that the immune response plays a part in the outcome of patients with SARS.^[1]

Binding and Entry

Coronaviruses bind to host cells primarily through interactions between viral spike glycoproteins and specific host cell surface glycoproteins. Some coronaviruses also bind to sialic acids on glycoproteins and glycolipids via their spike and/or hemaglutinin esterase glycoproteins. The interactions between coronaviruses and host cell receptors are critical determinants of species-specificity, tissue tropism, and virulence.^[1]

Replication

The infection cycle of coronavirus

Coronaviruses have single-stranded, positive-sense RNA genomes of about 30 kilobases, by far the largest non-segmented RNA virus genomes currently known. The key functions required for coronavirus RNA synthesis are encoded by the viral replicase gene. The gene comprises more than 20,000 nucleotides and encodes two replicase polyproteins, pp1a and pp1ab, that are proteolytically processed by viral proteases. Over the past years, it has become clear that the unique size of the coronavirus genome and the special mechanism that coronaviruses (and several other nidoviruses) have evolved to produce an extensive set of subgenome-length RNAs is linked to the production of a number of nonstructural proteins (nsps) that is unprecedented among RNA viruses. Many of these replicase cleavage products are in fact multidomain proteins themselves, thus further increasing the complexity of protein functions and interactions. Structural studies suggest that several nsps, following their release from larger precursor molecules, form dimers or even multimers. The various pp1a/pp1ab precursors and processing products are thought to assemble into large, membrane-associated complexes that, in a temporally coordinated manner, catalyze the reactions involved in RNA replication and transcription and, most probably, serve yet other functions in the viral life cycle.^[1][2]

Coronaviruses also exhibit ribosomal frameshifting and polymerase stuttering as part of their complex replicative cycle.^{[3][4][5][6][7]}

Genomic Cis-Acting Elements

In common with the genomes of all other RNA viruses, coronavirus genomes contain cis-acting RNA elements that ensure the specific replication of viral RNA by a virally encoded RNA-dependent RNA polymerase. The embedded cis-acting elements devoted to coronavirus replication constitute a surprisingly small fraction of the total genome, but this is probably a reflection of the fact that coronaviruses have the largest genomes of all RNA viruses. The boundaries of cis-acting elements essential to replication are fairly well-defined, and an increasingly well resolved picture of the RNA secondary structures of these regions is emerging. However, we are only in the early stages of understanding how these cis-acting structures and sequences interact with the viral replicase and host cell components, and much remains to be done before we understand the precise mechanistic roles of such elements in RNA synthesis.^[1]

Genome Packaging

The assembly of infectious coronavirus particles requires the selection of viral genomic RNA from a cellular pool that contains an abundant excess of non-viral and viral RNAs. Among the seven to ten specific viral mRNAs synthesized in virus-infected cells, only the full length genomic RNA is packaged efficiently into coronavirus particles. Studies have revealed cis-acting elements and trans-acting viral factors involved in coronavirus genome encapsidation and packaging. Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies and viral expression vectors based on the coronavirus genome.^[1]

References

External links

• Coronaviridae
• 19. Coronaviridae
• Coronaviruses
• Focus on Coronaviruses
• Viralzone: Coronaviridae