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Coronaviruses: Owner of the Largest RNA Genome

Coronaviruses are so-called positive strand RNA viruses, which means that on a number of essential points their molecular biology differs from that of "the cell". DNA does not play a role in their life cycle, which, moreover, does not involve the host cell's nucleus and takes place entirely in the cytoplasm. The virus particle contains a genome made of RNA (a nucleic acid similar to DNA but having different chemical properties), which, after the infection of the host cell, also serves as template for the synthesis of the first viral proteins, the so-called "replicase" (Ziebuhr et al., 2004). These proteins are for the most part viral enzymes that regulate the replication and expression of the genome.

The genome is copied into a complementary ("negative") RNA strand, which subsequently serves to produce new positive strands. Besides this process of genome replication, coronaviruses produce a number of subgenomic RNAs (RNA molecules representing a certain part of the genome) that are used to express the remaining genes in the viral genome (Pasternak et al., 2006; Sawicki et al., 2007). As is customary in positive strand RNA viruses, the complex involved in viral RNA synthesis is associated with modified membranes in the cytoplasm of the infected cell.

Coronaviruses - as shown in the electron micrograph on the left - thank their name to the "crown" of large projections on the surface of the virus particle. The scheme on the right shows the different components (genome RNA, proteins, and membrane) that make up a coronavirus particle.

Courtesy of Dr. Fred Murphy, Centers for Disease Control and Prevention (CDC), Atlanta, USA (left panel), and the Department of Medical Microbiology, Leiden University Medical Center, the Netherlands (right panel).

 

 

 

Among the protein products expressed from the subgenomic mRNAs are four proteins that are involved in the production of new virus particles: the nucleocapsid (N) protein that together with the RNA genome forms the core of the virus particle, and three envelope proteins (S, M and E), which can ultimately be found in the membrane of the virus particle that surrounds the nucleocapsid. Assembly of virus particles takes place when the nucleocapsid envelops itself in a small piece of host cell membrane taken from a compartment in the cytoplasm (de Haan & Rottier, 2005). These membranes already contain the viral envelope proteins, which are, therefore, immediately integrated into the virus particles. The S (for spike) protein forms the crown ("corona") of prominent protrusions from which the coronaviruses derive their name. The diameter of a coronavirus particle is approximately 120 nanometer (meaning that about 80,000 lined-up SARS virus particles would form a 1-cm long row).

The RNA genome of coronaviruses is special because of its length. Most positive strand RNA viruses have a genome of around 10,000 nucleotides (nucleotides are the building blocks of the RNA molecule; there are four different ones, abbreviated as A, C, G and U) and it is generally assumed that this restricted length is the result of the high mutation frequency, which is characteristic of all RNA viruses and is caused by the absence of a "proof reading" mechanism (a mechanism to correct errors) during RNA synthesis. The genome of coronaviruses, however, is 27,000 to 31,500 nucleotides long, making it the largest known RNA genome in biology. Coronaviruses are also known for their genetic variation and flexibility, which possibly originate in the special features indispensable to the survival of an RNA genome of such proportions (Gorbalenya et al., 2006).