Jumping Species: The origin
of the SARS coronavirus
Introduction
Throughout history, pathogenic microbes have demonstrated astounding ability
in adapting to new environments and changes in their host populations. When
necessary, many pathogens develop the ability to infect and spread in an entirely
new species. Once a pathogen evolves efficient modes of infection and
spreading in humans, it can lead to the epidemics that we have seen many times
before with infectious diseases such as smallpox, measles, diptheria, whooping
cough, and scarlet fever. As we find modes of prevention and treatment for
known diseases, new pathogens continue to arise as shown through outbreaks
of more recent epidemics including West Nile fever and SARS. The SARS (severe
acute respiratory syndrome) coronavirus was entirely new to humans when it
caused its first outbreak in the Guangdong province of Southern China in 2003.
Its novelty as a human pathogen can account for its rapid and deadly spread,
resulting in over 8,000 cases in 32 countries. The sudden appearance of SARS
also left researchers wondering where the microbe originated and how it
reached a new host in the human population.
The SARS coronavirus (SCoV) was presumed to be a zoonosis, a microbe which
has a natural animal host, but then jumps to humans. In order to determine the
possibility of animal hosts, a range of domestic and wild animals from a market
in the Guangdong province were examined.
Results
Fig. 1. SCoV-specific antibodies were detected in Himalayan palm civets or
HPC (SZ2 and SZ3) and Chinese ferret-badgers CFB (SZ17). Detection of
antibodies against recombinant nucleocapsid protein of SCoV in animal sera by
Western blot assay. A serum sample from a convalescent SARS patient (human)
was used as a positive control. Blots reacted with animal (SZ2 -HPC, SZ3 -HPC,
SZ11 -CFB, SZ17 -CFB, SZ7 -domestic cat, SZ16 -HPC, or SZ19 -Chinese hare) or
human sera are indicated. Results from the neutralization test for SCoV-specific
antibodies in these serum samples are also shown. SCoV-like viruses were
detected in HPC, CFB, and raccoon dogs. Electron microscopy of one infected
cell supernatant (SZ16) showed viral particles with a morphology compatible
with coronavirus which was used as an animal coronavirus for which
neutralization antibodies were analyzed.
Species tested, but not showing SCoV-like viruses included beaver, Chinese
muntjac, domestic cat, Chinese hare, and hog-badger.
Fig. 2. Animal SCoV-like viruses are separate phylogenetically from the
human virus cluster and within the animal cluster palm civet virus (SZ16) and
raccoon dog virus (SZ13) are almost genetically identical. Phylogenetic
analysis of the nucleotide acid sequence of the spike gene of SCoV-like viruses.
Nucleotide sequences of representative SCoV Sgenes were analyzed. The scale
bar shows genetic distance estimated using Kimura's two-parameter
substitution model (11). In addition to viruses sequenced in the present study,
the other sequences used in the analysis could be found in GenBank with
accession number: from AY304490 to AY304495, AY278741, AY278554,
AY278491, AY274119, and AY278489. Full-length genome sequencing of SZ16
showed 99.8% homology to human SCoV.
Table 1. Nucleotide sequence variation in 4 animal SCoV compared to 11 human
SCoV shows separation between human and animal strains. Nonsilent mutations
are highlighted in red. Dash indicates a nucleotide deletion. 38 nucleotide
polymorphisms were found between animal and human viral sequences, with 8
nucleotide differences between animal viruses and 20 nucleotide differences
between human viruses.
Conclusions
• Based on the presence of antibodies specific to SCoV in Himalayan palm civets and Chinese
ferret-badgers as well as SCoV-like viruses detected in both these species and raccoon dogs
(Fig. 1), of the animals tested these three species are potential sources of the spread of SCoV
to humans.
• There are phylogenetic distinctions between human SCoV and animal SCoV-like viruses (Fig.
2), but the 99.8% homology between the SZ16 (Himalayan palm civet) viral genome and that
of human SCoV show that they are closely related. Additionally, the genetic similarity between
SCoV-like viruses of Himalayan palm civets and raccoon dogs suggests possible contamination
or transmission between animals hosts.
•Nucleotide polymorphisms within human and animal virus groups, including the silent
mutations, show that the animal SCoV types found in the Guangdong province are just as
divergent as the human SCoV types isolated from different countries (Table 1).
•This study shows that the animals found in markets of the Guangdong province, specifically
Himalayan palm civets, Chinese ferret-badgers and raccoon dogs, are likely to have spread
SCoV to humans, sparking the SARS epidemic and supporting the hypothesis that the
appearance of SCoV was due to an interspecies transmission. It has yet to be determined if
these animals are the natural reservoir of the virus or if they are intermediate carriers
infected by another natural host.
References
Guan, Y., Zheng, B.J., He, Y.Q., et al., Isolation and characterization of viruses related to the SARS
coronavirus from animals in Southern China. Science 302: 276-8. 2003.
Crawford, Dorothy. Deadly Companions: how microbes shaped our history. Oxford University Press,
New York: 2007. Print.