Coronaviruses
COLLECTED BY
Organization:
Alexa Crawls
Starting in 1996,
Alexa Internet
has been donating their crawl data to the Internet Archive. Flowing in every day, these data are added to the
Wayback Machine
after an embargo period.
this data is currently not publicly accessible.
The Wayback Machine - https://web.archive.org/web/20070309144307/http://www-micro.msb.le.ac.uk:80/3035/Coronaviruses.html
Coronaviruses
Detailed notes
can be found in Principles of Molecular Virology.
|
Standard
Version
:
The 4th edition contains new
material on virus structure, virus evolution, zoonoses, bushmeat, SARS
and bioterrorism, CD-ROM with FLASH animations, virtual interactive tutorials
and experiments, self-assessment questions, useful online resources, along
with the glossary, classification of subcellular infectious agents and
history of virology. (
Amazon.co.uk
)
|
Instructors
Version
:
The 4th edition contains new
material on virus structure, virus evolution, zoonoses, bushmeat, SARS
and bioterrorism, CD-ROM with all the Standard Version content plus all
the figures from the book in electronic form and a PowerPoint slide set
with complete lecture notes to aid in course preparation. (
Amazon.co.uk
)
|
|
Introduction:
Coronaviruses were first isolated from chickens in 1937. After the discovery
of
Rhinoviruses
in the 1950's, ~50% of
colds still could not be ascribed to known agents. In 1965, Tyrrell and
Bynoe used cultures of
human ciliated embryonal
trachea
to propagate the first human coronavirus (HCoV) in vitro. There
are now approximately 15 species in this family, which infect not only man
but cattle, pigs, rodents, cats, dogs and birds (some are serious veterinary
pathogens, especially chickens).
|
Group IV: (+)sense RNA Viruses
|
Order
Nidovirales
- "Nested" Viruses
|
Family
(Subfamily)
|
Genus
|
Type Species
|
Hosts
|
Arteriviridae
|
Arterivirus
|
Equine arteritis virus
|
Vertebrates
|
Coronaviridae
|
Coronavirus
|
Infectious bronchitis virus
|
Vertebrates
|
Torovirus
|
Equine torovirus
|
Vertebrates
|
Roniviridae
|
Okavirus
|
Gill-associated virus
|
Vertebrates
|
The
Nidoviruses (Coronaviruses and Arteriviruses)
The ultimate book about coronaviruses, including virus-cell interactions, pathogenesis
and
vaccine
development.
This book should be studied by every virologist,
but the intricate replication strategies and other features of these viruses
are of general interest to all. Worth the expense
and highly recommended.
(
Amazon.co.UK
)
Morphology:
Coronavirus particles are irregularly-shaped, ~60-220nm in diameter, with
an outer envelope bearing distinctive, 'club-shaped' peplomers (~20nm long
x 10nm at wide distal end). This 'crown-like' appearance (Latin,
corona
)
gives the family its name. The centre of the particle appears amorphous in
negatively stained
EM preps,
the nucleocapsid being in a loosely wound rather disordered state.
|
|
The envelope carries three glycoproteins:
The genome is associated with a basic phosphoprotein,
N
.
Genome:
Non-segmented, single-stranded, (+)sense RNA, 27-31 kb (dependent on virus) -
the
longest
of
any RNA virus. The genome has a 5' methylated cap and 3' poly-A and functions
directly as mRNA (unlike (-)sense RNA viruses, no polymerase in particles!) -
but this
is a bit more complex than at first sight (below).
Replication:
Most human coronaviruses do not grow in cultured cells, therefore relatively
little is known about them, but two strains (229E & OC43) grow in some
cell lines & have been used as a model. Replication is slow compared
to other enveloped viruses, e.g. 24h c.f. 6-8h for
influenza
.
Entry occurs via endocytosis & membrane fusion (probably mediated by E2). Replication occurs in the
cytoplasm
.
Initially, the 5' 20kb of the (+)sense genome is translated to produce a viral polymerase, which then produces a full-length (-)sense strand (this step is poorly understood). This is used as a template to produce mRNA as a 'nested set' of transcripts, all with an identical 5' non-translated leader sequence of 72nt & coincident 3' polyadenylated ends:
Each mRNA is monocistronic, the genes at the 5' end being translated from the longest mRNA & so on. These unusual cytoplasmic structures are produced not by splicing (post-transcriptional modification) but by the polymerase during transcription. Between each of the genes there is a repeated
intergenic sequence
- UCUAAAC - which interacts with the transcriptase plus cellular factors to 'splice' the leader sequence onto the start of each ORF.
Assembly
occurs by budding into the golgi apparatus, particles being transported to the surface of the cell by the secretory nature of this organelle & released.
Pathogenesis:
These viruses infect a variety of mammals & birds. The exact number of
human isolates are not known as many cannot be grown in culture.
In humans, they cause:
- Respiratory infections (common), including Severe Acute Respiratory Syndrome
(SARS)
- Enteric infections (occasional - mostly in infants <12 months)
- Neurological syndromes (rare)
They are transmitted by aerosols of respiratory secretions, by the faecal-oral
route, and by mechanical transmission. Most virus growth occurs in epithelial
cells. Occasionally the liver, kidneys, heart or eyes may be infected, as well
as other cell types such as macrophages. In cold-type respiratory infections,
growth appears to be localized to the epithelium of
the upper respiratory
tract,
but there
is no adequate
animal
model
for
the human
respiratory coronaviruses. Clinically, most infections cause a mild, self-limited
disease (classical 'cold' or upset stomach), but there may be rare neurological
complications. SARS is a form of viral pneumonia where infection encompasses
the lower respiratory tract.
Coronavirus infection is very common and occurs worldwide. The incidence of
infection is strongly seasonal, with the greatest incidence in
children in
winter.
Adult
infections
are less
common.
The number
of coronavirus serotypes and the extent of
antigenic
variation
is unknown.
Re-infections
appear to occur throughout life, implying multiple serotypes (at least four
are known)
and/or antigenic variation, hence the prospects for immunization appear bleak.
Coronaviruses - the cause
of
SARS
SARS is a type of viral pneumonia, with symptoms including fever,
a dry cough, dyspnea (shortness of breath), headache, and hypoxaemia (low blood
oxygen concentration). Typical laboratory findings include lymphopaenia (reduced
lymphocyte numbers) and mildly
elevated
aminotransferase
levels (indicating liver damage). Death may result from progressive respiratory
failure due to alveolar
damage. The typical clinical course of SARS involves an improvement
in symptoms during the first week of infection,
followed by a worsening during the second week. Studies indicate
that this worsening may be related to patient's immune responses rather than
uncontrolled viral replication.
E.M of SARS virus
|
The outbreak is believed to have originated in February 2003 in the
Guangdong province of China, where 300 people became ill, and at least five
died. After initial reports that a
paramyxovirus
was
responsible, the true cause appears to be a novel coronavirus with some unusual
properties. For one thing, the SARS virus can be grown in Vero cells (a fibroblast
cell line isolated in 1962 from a primate) - a novel property for HCoV's,
most of which cannot be cultivated. In these cells, virus infection results
in a cytopathic effect, and budding of coronavirus-like particles from the
endoplasmic reticulum within infected cells.
|
SARS
War: Combating the Disease
In this book, the global SARS outbreak is traced and described, with a focus
on the regions where the most infections have been identified. An overview of
the whole saga is presented: how the disease spreads; how governments react;
how societies and people cope; and how health experts work fervently to identify
the virus and search for a cure. In addition, the book contains guidelines on
what a person or organisation can do to reduce the risk of contracting the potentially
deadly
illness.
(
Amazon.co.UK
)
The SARS virus is believed to be spread by droplets produced by coughing and
sneezing, but other routes of infection may also be involved, such as faecal
contamination, so wash your hands! In:
Donnelly
CA, et al. Epidemiological determinants of spread of causal agent of severe
acute respiratory syndrome in Hong Kong. Lancet volume 361, 03 May 2003
,
the authors report that:
- The most common reported symptom is fever (94%), with 51–72% of patients
reporting general influenza-like symptoms, chills, malaise, loss of appetite,
and myalgia. Gastrointestinal symptoms are less common at presentation, including
diarrhoea (27%), vomiting (14%), and abdominal pain (13%).
- The mean incubation period of SARS is estimated to be 6·4 days.
- The estimated case fatality rate is 13·2% for patients younger than
60 years and 43·3% for patients aged 60 years or older.
- Case clusters have played an important part in the course of the epidemic.
Amplification of short regions of the polymerase gene, (the most strongly
conserved part of the coronavirus genome) by reverse transcriptase polymerase
chain
reaction
(RT-PCR) and nucleotide sequencing revealed that the SARS virus is a novel
coronavirus which has not previously been
present in human populations. This conclusion is confirmed by
serological (antigenic) investigations.
We
now know the complete ~29,700 nucleotide sequence of many isolates of the SARS
virus
.
The
sequence appears to be typical of coronaviruses, with no obviously unusual
features, although there are some differences in the make up of the non-structural
proteins
which are unusual:
|
|
Lio
P, Goldman N. (2004) Phylogenomics and bioinformatics of SARS-CoV. Trends in
Microbiology. 12: 106-111
.
There is currently no general agreement that antiviral drugs
have been shown to be consistently successful in treating SARS or any coronavirus
infection. An
inactivated vaccine against SARS recently began clinical trials,
but even if successful will not be widelay available for a number of years.
New drugs targeted specifically against this virus are under development.
Diagnostic tests for coronavirus infection fall into two types:
- Serological
testing
for anti-coronavirus antibodies consists of indirect
fluorescent antibody testing
and
enzyme-linked
immunosorbent
assays (ELISA)
which detect antibodies against the virus produced in response to
infection. Although some patients have detectable coronavirus antibody
within 14
days of illness
onset,
definitive
interpretation
of negative
coronavirus antibody tests is possible only for specimens obtained >21
days after onset of fever.
- Molecular testing
consists of reverse transcriptase-polymerase
chain reaction (RT-PCR) tests specific for the RNA from this novel coronavirus.
This can detect infection within the first 10 days after the onset of fever
in some SARS patients, but the duration of detectable viraemia and virus
shedding is unknown, so RT-PCR tests performed too late could give negative
results. Commercial diagnostic tests are now available.
|
|
Emerging
Infectious Diseases (CD ROM)
A comprehensive collection from Emerging Infectious Diseases, a peer-reviewed
monthly
journal
tracking
and analyzing disease trends, published by the National Center for Infectious
Diseases of the Centers
for Disease Control. Includes:
Smallpox; Hantavirus; Dengue Hemorrhagic Fever; West Nile Virus; Influenza;
Rhabdoviruses; Simian Immunodeficiency
Viruses; Hepatitis; Ebola; AIDS/HIV; Rift Valley Fever, & much more.
Where did the SARS virus come from?
Coronaviruses with 99% sequence similarity to the surface spike protein
of human SARS isolates have been isolated in Guangdong, China, from apparently
healthy masked palm civets (
Paguma larvata
), a cat-like mammal closely related
to the mongoose. The unlucky palm civet is regarded as a delicacy in Guangdong
and it is believed that humans became infected as they raised and slaughtered
the animals rather than by consumption of infected meat.
|
|
Might SARS coronavirus recombine with other human coronaviruses to produce
an even more deadly virus? Fortunately, the coronaviruses of which we are aware
indicate
that recombination has not occurred between viruses of different groups, only
within a group, so recombination does not seem likely given the distance between
the
SARS virus and HCoV.
There is considerable experience of development of coronavirus vaccines for
veterinary purposes – though not all of it is encouraging. On the whole,
inactivated coronavirus vaccines induce poor protection. The spike protein alone
can induce immunity, but the internal nucleoprotein has also been reported to
induce protective immunity. The WHO has recommended that SARS vaccines be developed.
The quickest and probably safest to develop would be an inactivated or subunit
vaccine. Even if such a vaccine were not fully protective against SARS infection,
it might still provide some protection against life-threatening SARS pneumonia.
Current SARS Information & News from:
Virus
X: Tracking the New Killer Plagues
Frank Ryan.
Who needs Stephen King when there are such real-life
horrors as those described in this book to keep sleep at bay? A well-written
study that reads more like
a thriller than a science book. The heroes are the doctors, nurses, and patients
on the frontlines of plague as well
as the researchers at laboratories such as the Centers for Disease Control in
Atlanta, Georgia; the enemies are the myriad new viruses and virulent new strains
of old viruses that are emerging in ever greater numbers.
(
Amazon.co.UK
)
Coronaviruses - the cause of
Kawasaki
disease
?
Kawasaki disease is a childhood illness which mostly affects
children under five years old. It is the leading cause of acquired heart disease
in children. Earlier publications have suggested the involvement of a novel coronavirus
in Kawasaki Disease:
but more recent studies have not supported the association between the HCoV-NL63
virus and Kawasaki disease:
DISCLAIMER
Biological Sciences
©
Microbiology @ Leicester
2006.