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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.
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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).
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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).
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