Coronaviridae   (Under Construction)

Table of Contents

 

Coronaviridae Family

The Coronaviridae family consists of two genera - coronavirus and torovirus - and a possible third, arterivirus. The toroviruses infect humans and animals and are predominantly associated with enteric disease. Toroviruses have been associated with enteric disease of horses (Berne virus), cattle (Breda virus), pigs, and cats. The virions have a typical pleomorphic morphology and virion organization is characteristic of the Coronaviridae family.  The coronavirus genus contains many important pathogens of veterinary significance and is described below: the arterivirus genus, which has tentatively, and probably only temporarily, been placed in this family.

Coronaviruses infect a wide range of mammals (including humans) and birds. They exhibit a marked tropism for epithelial cells of the respiratory and enteric tracts. In addition to such infections, other diseases caused by coronaviruses include hepatitis, neurologic disease, infectious peritonitis, nephritis, pancreatitis, runting, and adenitis. These viruses are divided into three antigenic groups: porcine transmissible gastroenteritis virus, canine and feline coronavirus, and feline infectious peritonitis virus constitute Group I; porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, and turkey coronavirus make up Group II; and infectious bronchitis virus is comprised by Group III.

Coronavirus has a unique morphologic appearance characterized by large club-shaped surface projections (peplomers) extending out of a somewhat pleomorphic lipidcontaining envelope that encloses a coiled helical nucleocapsid structure. Virion size ranges from 75 nm to 160 nm in diameter, and the genome consists of a single molecule of ssRNA (positive sense).

Two viral-specified structural glycoproteins (S and M) are found in the envelope. Glycoprotein S is largely external to the membrane perimeter and gives rise to the typical club-shaped projections (approximately 20nm in length) of the virion membrane. The glycoprotein contains epitopes to which neutralizing antibodies and cell-mediated cytotoxicity are directed and is responsible for virion binding to host cell membranes. Glycoprotein M is a transmembrane molecule and is more deeply embedded in the envelope. Antibodies directed against M may neutralize the virus in the presence of complement. The third major structural protein is a basic phosphoprotein (N) that forms a long, flexible,, helical nucleocapsid enclosing the genomic RNA.

 

Properties of Coronaviruses

The coronaviruses were so named because the unusually large clubshaped peplomers projecting from the envelope give-the particle the appearance of a solar corona. Though typically about 100 nm in diameter, the virion is pleomorphic and can range in size from 75 to 160 nm. The helical ribonucleoprotein, difficult to discern in electron micrographs, is composed of the genomic RNA and the phosphorylated nucleocapsid protein N (50K-60K). The envelope includes a lipid bilayer derived from intracellular membranes of the host cell and three types of glycoproteins, M (E 1, 23K-29K), HE (E3, 62K-65K, absent in some coronaviruses), and S (E2, 170K-220K). M (El) is a transmembrane protein that performs the role filled by the matrix protein in other enveloped viruses. The large peplomers are composed of S (E2) which binds to cellular receptors, causes membrane fusion, and induces the production of neutralizing antibodies. HE (hernagglutinin esterase, E3), which is found particularly in the antigenic group II coronaviruses, binds to erythrocytes of some species and has receptor-destroying (acetylesterase) activity.

The genome consists of a single linear molecule of plus sense ssRNA, 27-33 kb (the largest of all RNA virus genomes), which is capped and polyadenylated. Viral RNA is infectious.

The family contains one genus, Coronavirus, which has been divided into four antigenic groups (I [Mammalian]. II [Mammalian], III [Avian], IV [Avian]). Viruses within each group show some antigenic cross-reactivity, and there may be a number of serotypes within one virus species. Animals immune to one serotype are susceptible to infection with different serotypes of the same coronavirus.


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Properties of Coronaviruses

 

  • Pleomorphic spherical virion, 75-160 nm (average 100 nm) in diameter
  • Envelope with large, widely spaced, club-shaped peplomers
  • Tubular nucleocapsid with helical symmetry, 1020 nm in diameter
  • Linear plus sense ssRNA genome, 27-33 kb, capped and polyadenylated, infectious
  • Three or four structural proteins: peplomer glycoprotein S (E2, 18OK220K),
      transmembrane glycoprotein M (El, 23K-29K), nucleocapsid phosphoprotein N
      (50K-60K); some viruses have peplomers with hernagglutinin plus acetylesterase activity, HE (E3, 62K-65K)
  • Replicates in cytoplasm; full-length minus sense RNA strand is transcribed from the virion RNA, from which a nested set of mRNAs is produced with unique sequences at their 5' ends, which are translated; maturation is by budding into endoplasmic reticulum and Golgi cisternae, with virions released by exocytosis.

Right. Electron photomicrograph of feline infectious peritonitis virus. The electron-dense RNA core is surrounded by radiating petal-shaped spikes peplomers, which give the virus its typical corona appearance.

Electron photomicrograph_of_feline _nfectious_peritonitis_virus.jpg (494023 bytes)

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Viral Replication

The whole of the replication cycle occurs in the cytoplasm and is relatively slow. Following adsorption, penetration, and uncoating, the input virion RNA molecule is translated directly, one of the products being an RNA polymerase which then transcribes a full-length minus sense RNA, from which is transcribed a 3'-coterminal "nested set" of subgenomic mRNAs.   The nested set comprises five to seven overlapping species of mRNAs which extend for different lengths from a common 3' terminus. The genomic RNA and all mRNAs have an identical 5'leader sequence of about 72 nucleotides. Accordingly, the nested set of mRNAs is formed by the unusual mechanism of joining two noncontiguous RNAs. The joining of the 5' leader sequence to the remaining part of each mRNA occurs during transcription. Probably multiple copies of the 5' leader RNA are synthesized independently, following which they bind to complementary intragenic initiation sites on the (-) strand RNA where they are linked to form each member of the nested set. Only the unique sequence toward the 5' end, which is not shared with the next smallest mRNA in the nested set, is translated, each product therefore being a unique protein.

The translation of the structural proteins M, S, and N is associated with maturation of virions by budding into vesicles formed from the rough endoplasmic reticulum and Golgi apparatus. The S protein, which is glycosylated cotranslationally, and the M protein, which is glycosylated in the Golgi apparatus, become inserted in the vesicle membrane and serve as sites for association with nucleocapsid. Virions are released by exocytosis when the virion-filled vesicles fuse with the plasma membrane.

Coronavirus transcription and translation.
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 Coronavirus__ranscription_and_translation.jpg (54367 bytes)

After release of the (+) strand genomic RNA in the cytoplasm, an RNA-dependent RNA polymerase is synthesized, which transcribes a full-length (-) strand RNA, from which are synthesized (a) new genomic RNA, (b) an overlapping series of subgenomic mRNAs, and (c) leader RNA. The genomic RNA and mRNAs are capped and polyadenylated (zigzag line) and form a "nested set" with common 3' ends and a common leader sequence on the 5' end. Only the unique sequence of the mRNAs toward the 5' end is translated, to produce several nonstructural proteins (NS) and four structural proteins: M (EI), transmembrane glycoprotein; S (E2), peplomer glycoprotein; N, nucleoprotein; and in some coronaviruses HE (E3), hemagglutinin-esterase glycoprotein. Maturation and assembly occur in the rough endoplasmic reticulum and the Golgi, and virions are released by exocytosis. [Modified from K. V. Holmes, In "Fields Virology" (B. N. Fields et al., eds.), 2nd Ed., p. 847. Raven, New York, 1990.1

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Diseases Caused by Coronaviruses

 
Feline Infectious Peritonitis

Feline infectious peritonitis is an important disease that occurs in cats of all ages and in all parts of the world. Serologic surveys have established that the virus is widely distributed in wild and domestic cats. For example, in catteries it is not unusual to find over 90% of cats with antibody to the virus. However, the incidence of clinical disease is much lower (<10%), indicating that subclinical infections are common.

Feline infectious peritonitis often occurs in association with other diseases, particularly those likely to cause immunosuppression, such as feline leukemia, feline immunodeficiency, feline panleukopenia, and feline syncytial virus infections. A second feline coronavirus that causes diarrhea may be a variant of infectious peritonitis virus with a tropism for the epithelial cells of the intestine.

Clinical Features. The clinical onset of feline infectious peritonitis is insidious; the cat loses its appetite, is depressed, and may have a fever. Progressive debility follows, and in the classic ("wet") form of the disease, abdominal distention is seen as a result of the peritonitis, although only a proportion of clinically diseased cats develop peritonitis. Pleuritis causing dyspnea is observed in some cats, and there are reports of neurologic and ocular disease, occurring in others. Affected cats die within 1 to 8 weeks. Peritoneal fluid from cats with peritonitis clots, contains high concentrations of protein, and is often flecked with fibrin.

Pathogenesis and Pathology. FIP is caused by a rare mutant form of a ubiquitous feline enteric coronavirus. The enteric coronavirus infection ivolves virtually all cats, and especially cats from shelters and purebred catteries. The mutation, when it occurs, is usually during the initial enteric coronvirus infection. and the disease incubates for days, months and even years before becoming clinical. Cats with FIP usually do not shed FIP virus, because the mutant virus is present only in the lesions within the body. The only virus that most of them shed is the parent enteric coronavirus. This means no two cases of FIP are caused by the same virus, and that horizontal transmission, i.e., cat-to-cat transfer is rather the exception than the rule. Because the mutation to FIP virus is uncommon, other cats exposed to a cat with FIP have the same low risk of developing FIP as any cat infected with enteric coronavirus.

Diagnosis. Clinical diagnosis of the classic ("wet") form of feline infectious peritonitis is not difficult. When doubt exists, virus isolation from peritoneal exudates, blood, and homogenates of abdominal and thoracic organs can be attempted in feline embryonic lung cultures. Antibody can be detected in sera by several techniques, but in view of the frequency of inapparent infections with infectious peritonitis virus, interpretation of such data is difficult. A polyclonal hypergammaglobulinemia in the presence of appropriate clinical signs can aid diagnosis.

Epidemiology and Control. Under natural conditions, feline infectious peritonitis virus probably spreads by aerosol from clinically diseased cats. The roles of fecal excretion of the virus and subclinically infected cats in the epidemiology of the disease have not been critically examined. The fact that some cats with actively or passively acquired antibody develop a more rapidly progressive form of the disease than seronegative cats inoculated with the same dose of virus represents a major hurdle to the development of effective vaccines. Control of feline infectious peritonitis depends on segregation of infected cats. Any cat with antibody to the virus must be regarded as persistently infected.


Taxonomy

Virus Code. 19. Virus Accession number 19000000.

Virus infects vertebrates.

Description is on taxonomic level of family. Virus belongs to the order Nidovirales (VC VO03. ).

 

Properties of Virion

Morphology

Virions enveloped; slightly pleomorphic; spherical, or kidney-shaped, or rod-shaped; 120-160 nm in diameter, or
120-140 nm in diameter. Surface projections of envelope distinct; club-shaped; spaced widely apart and
dispersed evenly over all the surface. Nucleocapsids rod-shaped (straight or bend); 9 nm in diameter, or 11-13
nm in diameter. Symmetry helical (or tubular).

 

 

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