MicrobiologyBytes: Virology: Coronaviruses Updated: April 8, 2009 Search

Coronaviruses

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Detailed notes can be found in Principles of Molecular Virology.

CoverStandard 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)

Cover 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

 

CoverThe 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. Coronavirus particle

The envelope carries three glycoproteins:

The genome is associated with a basic phosphoprotein, N.

Coronavirus particle

 

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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:

Coronavirus 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:

Coronavirus transcription

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:

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.

SARS virus
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.

CoverSARS 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:

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: Coronavirus dendrogram

Sars Genome

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:

  • 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.
Test kit

CoverEmerging 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.

Palm Civet

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:

 

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Frank Ryan.

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(Amazon.co.UK)

SARS: Latest news

 

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:



© MicrobiologyBytes 2009.