Summary
Researchers in Rotterdam have positively identified the virus responsible for SARS
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Recent reports over the last couple of weeks have claimed that SARS, a
new type of highly contagious and occasionally fatal viral pneumonia,
may be caused by a paramoxyvirus, maybe by a coronavirus, and maybe by
chlamydia. Dutch scientists at Erasmus Medical Center in Rotterdam,
the Netherlands today announced that SARS is indeed caused by a novel
form of coronavirus never before seen in humans. The World Health Organization (WHO) has confirmed
this report. Experiments revealed that monkeys infected with
coronavirus develop symptoms similar to those seen in the human
syndrome, those that are not infected do not develop the symptoms, and
those infected with both paramoxyvirus and coronavirus are no sicker
than those infected with coronavirus alone. These criteria are
considered to be definitive proof that the newly-identified
coronavirus is indeed the causative agent of SARS.
Coronaviruses cause disease in both humans and animals. Although
there are only two coronaviruses that infect humans, they are
responsible for an estimated 1/3 of all colds. Coronaviruses also
cause diseases, some of which are serious, in animals.
The first clinical cases of SARS appeared in China in November of
2002, and only in the past few weeks has SARS attracted international
attention. Yet scientists have not only identified the new pathogen,
but its genome has been independently sequenced at
the University of Hong Kong
(report from People's Daily) and at the
Centers for Disease Control
in Bethesda, MD (CDC SARS information
page).
The complete SARS virus sequence was
published in GeneBank on Tuesday (April 15, 2003). It's astonishing how
quickly the research community has been able to identify and
characterize this new pathogen.
The SARS coronavirus is formed of 29736 bases of (+)-sense,
single-stranded RNA (ssRNA). The virus enters the cell through
endocytosis and membrane fusion, and releases mature mRNA into the
cytosol, where its first 20 kb is translated into a viral
polymerase. The polymerase then creates a full-length (-)-sense
strand, that codes for several proteins. The (-)-sense mRNA is then
used as a template to create several other monocistronic mRNAs that code for viral
proteins. The proteins assemble in Golgi and are exocytosed through
the secretory pathway.
Sequencing the genome for SARS has several benefits:
Although the origin of SARS is as yet unknown, phylogenetic analysis
of the sequence indicates that it is a new virus that has not been
seen in humans before. Scientists believe that the virus has probably
been in an animal population for quite some time, but the original
host has not yet been identified.
Studying the sequence has already lead scientists to believe that
there is little or no evidence that SARS is a bioweapon.
In the short term, having the SARS sequence allows design of sensitive
polymerase chain reaction (PCR) tests that can rapidly identify
presence of the SARS virus itself. Existing serological tests look for
antibodies to the virus, but by the time the antibody titers are high
enough to be detected (typically three weeks following the onset of
fever), it is often too late for the patient. By contrast, the SARS
RT-PCR test should work within the first ten days of onset of fever.
A positive PCR test for SARS indicates positively that a patient is
infected. A negative test cannot rule out exposure or infection for a
variety of reasons. For example, the sample taken from the test may
not have contained the virus, or the virus may be suppressed by the
host's immune system.
Knowing the sequence may help researchers to study how the virus is
transmitted, to detect the viremia and virus shedding timeline, and to
develop effective quarantine strategies.
In the long term, understanding SARS may help researchers discover a
way to combat the disease, or at the very least, to predict who is
likely to be at greatest risk. While 96% of SARS patients recover
spontaneously, those over 40 or with existing heart or liver
disease are most at risk for SARS.