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The analysis of the phylogeny of viruses
(the reconstruction of their ancestry
on the basis of their genome sequences) can yield important
information with regard to the rate of virus evolution and genetic changes
that lie at the base of the altered features of a virus. The position of
the coronavirus family is fairly complex in terms of evolution and
taxonomy. The family is currently divided into two genera (Coronavirus and
Torovirus) and the Coronavirus genus is further divided into groups 1 to 3,
with group 3 viruses infecting birds. Given the many new coronaviruses
discovered over the past years, further subdivisions and/or the creation of
new groups are likely in the near future. Moreover, the family
Coronaviridae belongs to the virus order Nidovirales (Gorbalenya et al., 2006), which also
comprises two other virus families, Arteriviruses and Roniviruses. These
families have been combined on the basis of the (deduced) common ancestry
of their replicase proteins, strikingly similar genome organisations and
similar genome expression strategies. On the other hand, the virus
particles and structural proteins of these three Nidovirus families are
totally different and the viruses cause diverse kinds of infections.
Although the Arteriviruses known so far, like Coronaviruses, (primarily)
infect mammals, Roniviruses have been isolated from prawns.
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Courtesy
of the Department of Medical Microbiology, Leiden
University Medical
Center, the Netherlands.
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Immunofluorescence assay of
SARS-CoV-infected Vero-E6 cells stained with an antiserum from a SARS
patient (left panel) and an antiserum raised in rabbits that recognizes
one of the replicase components, thereby revealing the site of viral RNA
synthesis in the infected cell.
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Due to the fact that there are no
fossils of viruses, it is extremely difficult to reconstruct virus
evolution in detail or to deduce the time scale at which it has occurred.
It is evident, however, that the Nidoviruses have come a long way, during
which the core of the replicase gene has been preserved. This has also
resulted in the preservation of the organisation of the viral genome and
its expression strategies. At the same time, the structural proteins and
biological characteristics of Nidoviruses have diverged considerably.
Mutation and selection have obviously played a part in this, but it is
generally assumed that greater leaps have also been made. RNA viruses are
capable of exchanging larger amounts of genetic information through RNA
recombination (the "mixing"
of genome parts from different viruses into a new genome variant).
Several indications for the occurrence of this process have already been
found in the genomes of present-day Coronaviruses. Similarly, the preserved
replicase gene may in the past have been connected to totally different
sets of structural protein genes. It has been postulated that the
transcription mechanism that is used to produce subgenomic mRNAs may have
played an important part in these great leaps in evolution.
Minor genetic changes can have great impact
Several examples are known of
Coronaviruses in which relatively minor genetic changes have apparently had
a major impact on the biology of the virus. A reasonable case has been made
for the fact that changes in the Spike (S) protein of porcine coronavirus
have in the past led to an altered tropism (specificity for a particular cell or tissue type or a particular
host), whereby the virus changed from a respiratory pathogen to
a virus capable of infecting the gastrointestinal tract. Evolution can also
go hand in hand with the transfer to a different host, and it seems
plausible that this is the case, for instance, for the human coronavirus
OC43, which is remarkably closely related to the bovine coronavirus. This
indicates that SARS-CoV is probably not the first coronavirus to transfer
from an animal to a human host. Any such transfer is followed by a crucial
phase in which the virus needs to demonstrate or develop the potential to
spread efficiently from human to human, a phase that is difficult to fathom
and can at best be reconstructed in retrospect on the basis of genetic
sequences obtained from animal and human virus isolates. In principle, a
small number of point mutations in the genome (a change of a single nucleotide into another one,
resulting in a single change in one of the viral proteins) can produce decisive
differences in the properties of viral proteins, resulting, for instance,
in the capability to efficiently bind a new receptor (a cell surface molecule "abused" by
the virus for entering the host cell) or in the ability to
replicate in cells of the new host. In the case of SARS-CoV, evidence has
accumulated suggesting an important role for the acquisition of such point
mutations in the S protein (The Chinese SARS Molecular
Epidemiology Consortium, 2004), optimizing the interaction with the ACE-2 receptor
(Li et al., 2003) for the virus on
the surface of human cells and thereby improving the efficiency of
human-to-human transmission.
Reconstruction of the spread of SARS-CoV
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