This document provides information on the Coronaviridae family of viruses. It discusses that coronaviruses are enveloped, positive sense RNA viruses that cause respiratory, enteric, hepatic and neurological diseases in humans and animals. Examples of animal diseases caused by different coronavirus genera include transmissible gastroenteritis in pigs, feline infectious peritonitis, canine respiratory coronavirus, mouse hepatitis virus, and avian infectious bronchitis. The document also covers virus properties, replication, pathogenesis of diseases, and host immune responses to coronavirus infections.
2. Coronaviridae
is the family of RNA viruses which include:
1-coronaviridae
2-Arteriviridae 3-Roniviridae
• -enveloped
• -linear positive sense single stranded RNA
• Cause acute and chronic infection in human and a wide variety of animals resulting in
respiratory, enteric, hepatic and neurologic disease of varying degrees of severity.
• Sever acute respiratory syndrome (SARS) emerged from china untreatable human
respiratory disease certain species of bats were identified as reservoir hosts of the virus.
• They exhibit a marked tropism for epithelial cells of the respiratory and enteric tracts, as
well as macrophages of some animals.
• They typically have the capacity to cross the species barrier (species jumping) and infect new
hosts.
3. Diseases:
• Avian infectious bronchitis virus (IBV) was the first coronavirus to be isolated from
chicken embryos in 1937.
• Mouse hepatitis virus (MHV)
• Porcine transmissible gastroenteritis virus (TGEV)
• Bovine coronavirus (BCoV)
• Feline coronavirus
• Human coronaviruses (HuCoV)
4. The genus coronavirus is divided into three groups(1-3)
based on their serologic cross-reactivity:
• 1-Alphacoronavirus mammalian coronaviruses
• 2-Betacoronavirus
• 3-gammacoronavirus: avian coronaviruses
• 4- Deltacoronavirus.
5. The increased diversity of coronaviruses in Bats and birds could be due to several reasons:
• 1-bats and birds are highly diverse species. Bats represent 20% of the 5742 mammalian species and there
are about 10000 bird species around the world.
• 2-bats and birds can fly far distances. This would allow bats and birds to exchange viruses with different
species that come in close contact.
• 3-different environmental pressures (climate, food, shelter and predators).
• 4- the habit of roosting (bats) and flocking (birds) in large numbers will facilitate exchange of viruses
among individual bats and birds.
6. Virion Properties and Virus Replication
• Coronaviruses have aunique morphologic appearance of acrown and the name“coronavirus”
was derived from the Latin word corona(Greekκoρωνα),meaning crown.
• Virions are pleomorphic or spherical (genus Coronavirus)
Virions are enveloped, with large club-shaped spikes (peplomers)
The genome consists of a single molecule of linear positivesense
• Coronavirus virions contain three or four structural proteins:
a major spike glycoprotein (S),
• transmembrane glycoproteins(M and E),
• a nucleoprotein (N),
• and, in some viruses, a hemagglutinin esterase (HE).
• Viruses replicate in the cytoplasm
7. • E protein protein, together with the M protein, plays an essential role in coronavirus
particle assembly.
• The S glycoprotein forms the large peplomers on the virion surface, giving the virus its
corona or crown-like morphology when examined under the electron microscope.
• The S protein of coronaviruses has several biological properties that include:
• binding to specific cellular receptor(s),
• inducing neutralizing antibodies, eliciting cell-mediated immune response, inducing fusion
of the viral envelope with host cell membranes, inducing cell–cell fusion, and binding the
Fc fragment of immunoglobulin (MHV and TGEV).
8. HE protein of coronaviruses has several
biological properties and these include:
hemagglutination, hemadsorption,
• the esterase activity that cleaves acetyl groups from 9-Oacetyl-neumeric acid, and may
play a role in initial virus adsorption and entry or release from the infected cells.
• The M protein of coronaviruses interacts with both the N and S proteins and may
play a key role in virus assembly. It may also play a major role in packaging viral RNA
into nucleocapsids during virus assembly.
9. • The E protein of coronaviruses acts synergistically with the M protein during
virus budding from the infected cells. In addition to this, E protein also
functions as an ion channel.
• The N protein interacts with the viral genomic RNA to form the viral
nucleocapsid. The N protein has three relatively conserved structural
domains and it interacts with M protein, leading to the incorporation of the
nucleocapsid into the virus particle
10. Toroviruses
• Toroviruses are pleomorphic :Spherical, oval elongated, and kidney-shaped particles have
been visualized under EM. enveloped with a tubular nucleocapsid of helical symmetry.
• The nucleocapsid forms a doughnut-shaped structure and the envelope contains a large
number of small spikes that resemble the peplomeres of coronaviruses.
• Torovirus particles consist of at least four structural proteins:
nucleocapsid protein (N), unglycosylated membrane protein (M), spike glycoprotein (S), and
HE protein.
• positive-sense, linear molecule of ssRNA.
• Virus infectivity is stable between pH 2.5 and 9.7 but rapidly inactivated by heat, organic
solvents, and irradiation.
11. Bafinivirus
• The WBV has a bacilliform shape with an envelope containing coronavirus-
like spikes
• The virion consists of a rod-shaped nucleocapsid surrounded an envelope
that
consists of glycosylated S protein and integral membrane protein M.
The virus replicates in various fish cell lines. and sensitive to lipid solvents.
12. Animal Diseases Caused by Members of the
Genus Alphacoronavirus
• 1-Transmissible Gastroenteritis Virus and Porcine Respiratory Coronavirus Disease.
Transmissible gastroenteritis (TGE) is a highly contagious enteric disease of swine caused by TGEV.
TGEV can antigenically cross-react with porcine respiratory coronavirus (PRCoV).
TGEV is characterized by severe diarrhea, vomiting, dehydration, and high mortality in young piglets
(less than 2 weeks of age). Mortality in older pigs (greater than 5 weeks) is usually low.
Most of the time TGEV infection of adult swin is asymptomatic, but sometimes infected sows exhibit
anorexia, diarrhea, fever, vomiting, and agalactia. More than 25 years ago, PRCoV was detected in swine
herds with minor respiratory symptoms that are closely related to TGEV.
13. Pathogenesis and Pathology
• . TGEV survives in the gastrointestinal tract after ingestion because of its resistance
to low pH and trypsin, thus it passes through the stomach without inactivation. viral
replication occurs in villus epithelial cells of the small intestine with highest titers of
virus in the jejunum.
• TGEV infects and destroys the columnar epithelial cells lining the intestinal villi,
resulting in atrophy of the villi. Occurrence of severe diarrhea .The loss of
enterocytes lining the villi results in malabsorption and maldigestion.
14. • The PRCoV is transmitted via respiratory aerosols and droplets to susceptible in-
contact animals. The virus replicates in the tonsils, mucosal epithelium of the nasal
passage and the airways of the lungs This cause inflammation and necrosis of
terminal airways of the lungs leading to diffuse broncho interstitial pneumonia. The
severity of clinical signs and lesions may vary and subclinical infection can occur in
herds.
15. Host Response to Infection:
• Neutralizing antibodies develop within approximately 7 days of TGEV infection of swine.
The presence of secretory IgA plays a major role in protective immunity and viral clearance.
• Intramuscular immunization of pigs with TGEV results in development of a humoral IgG
response but not protective immunity. Conversely, pigs immunized orally with TGEV
develop protective virus-specific IgA in their intestinal mucosal secretions.
• Infection of sows with TGEV results in the secretion of protective IgA in colostrum (so-
called lactogenic immunity), which is protective in suckling pigs. High levels of type I
interferon are produced by infected intestinal cells, which also may play a role in controlling
viral replication.
16. • 2-Porcine Epidemic Diarrhea Virus
• Coronavirus-like viruses have been isolated from swine with diarrhea, thus
their designation as porcine epidemic diarrhea viruses (PEDV). These
viruses are antigenically distinct from TGEV and porcine hemagglutinating
encephalomyelitis virus (PHEV), and cause diarrhea, vomiting, and dehydration
in inoculated swine.
17. 3-Canine Enteric Coronavirus Disease.
• Canine coronavirus (CCoV) infects domestic and wild canine species and the first
CCoV was isolated from dogs with acute enteritis. CCoV infection of dogs is highly
contagious and generally causes inapparent or mild gastroenteritis.
• CCoV is an important entero pathogen of dogs and is widespread in dog populations,
mainly in kennels and animal shelters.
18. • The virus is shed at high titers in the feces of infected dogs leading to typical fecal-
oral route of transmission characterized by high morbidity and low mortality.
• Fatal infection usually occurs as a consequence of mixed infections with CCoV
together with canine parvovirus type-2, canine adenovirus type-1, or canine
distemper virus.
• CCoVs are inactivated by lipid solvents and are heat-labile. The viruses are acid-
stable (pH of 3.0) and retain infectivity under cool conditions.
• Incubation period of 1–4 days mortality is typically very low.
19. 4-Feline Infectious Peritonitis and Feline
Enteric Coronaviurus Disease.
• Feline infectious peritonitis(FIP)is acontagious, progressive, and highly fatal
disease of domestic and some wild feline species. The signs are highly
variable and reflect the tissues affected by the disease, but persistent fever,
• weight loss, lethargy, dyspnea, and abdominal distension are all common
clinical signs. The disease can occur in cats of all ages but is especially
common in young and very old cats.
20. • Two distinct forms of FIP are recognized:
• (1)an effusive (wet) and (2) a non effusive (dry) form.
• The effusive form, which is two to three times as common as the dry form, is
characterized by accumulation of protein-rich fluid (exudate)in the peritoneal cavity.
The non effusive form is characterized by formation of granulomas in internal
organs, central nervous system (CNS), and eyes.
• Mortality rates are high.
21. • FIP has an unusual and highly complex pathogenesis that involves the
mutation of relatively apathogenic feline enteric coronavirus (FCoV) into
FIPV that replicates in macrophages to produce an immune-mediated
disease in affected cats. The FIPV efficiently infects macrophages and
monocytes that escape from the intestine to cause lethal systemic disease
with multiorgan involvement, in classical cases accompanied by accumulation
of abdominal exudate (ascites)
22. • FCoV and FIPV occur worldwide. FCoVspreads efficiently via the fecal-oral
route but in contrast, FIPV is not well transmitted. FCoV may persist sub clinically
for up to a year or longer and these persistently infected cats serve as the virus
reservoir that allows horizontal spread between cats
23. • 5-Ferret Coronavirus
• Recently a novel ferret enteric coronavirus (FRECV) was identified in
domesticated ferrets (Mustela putorius furo) associated with epizootic
catarrhal enteritis (ECE).
24. 6-Rabbit Coronavirus
• Rabbit coronavirus (RbCoV) infection was first reported in 1961 by Scandinavian
researchers who observed 50−75% mortality among laboratory rabbits. It was
established that acute RbCoV infection targets the heart and results in virus induced
myocarditis and congestive heart failure in rabbits.
• Antiserum to RbCoV cross-reacts with FIPV, CCoV, and TGEV by
radioimmunoassay.
25. Animal Diseases Caused by Members of the
Genus—Betacoronavirus
• 1-Porcine Hemagglutinating Encephalitis Virus:
• PHEV is the cause of vomiting and wasting disease (VWD) of young swine that is
characterized by encephalomyelitis, vomiting and wasting.
• PHEV is antigenically related to BCoV. The virus hemagglutinates chicken, rat, mouse,
hamster, and turkey erythrocytes.
• PHEV is sensitive to lipid solvents, including sodium deoxycholate; it is also heat labile and
relatively stable when frozen. VWD occurs in pigs less than 3 weeks of age, although older
swine may exhibit milder signs of the disease. Mortality is high, up to 100%; pigs also may
develop chronic infections and eventually die from starvation or secondary infections. Nasal
secretions contain virus and horizontal aerosol
• And direct animal contact are mechanisms of transmission.
26. 2-Bovine Coronavirus
• BCoV is a pneumoenteric virus that infect upper and lower respiratory tracts, as well as
the intestine of cattle and wild ruminants.
• In cattle, BCoV can cause three different disease syndromes: neonatal diarrhea in
newborn calves (1–3 weeks, calf diarrhea (CD)) and winter dysentery (WD) in adult
cattle with hemorrhagic diarrhea and respiratory infections in cattle of various ages.
• The respiratory infections in cattle include shipping fever or bovine respiratory disease
complex (BRDC) in feedlot cattle.
• Respiratory disease caused by RBCoV typically occurs in calves aged 6–9 months, and
is characterized by fever, nasal discharge, and respiratory distress
27. • BCoV is acid stable (pH of 3.0), but is inactivated by lipid solvents, detergents, and high
temperatures. Although there are significant phenotypic, antigenic and genetic differences
between EBCoV and RBCoV strains, the precise relationship between enteric and respiratory
strains of BCoV is uncertain.
• The distribution of BCoV is worldwide, and transmission of EBCoV is likely fecal-oral by
ingestion of virus from contaminated feed, teats, and fomites. RBCoV is shed in respiratory
tract secretions of infected animals, and thus is spread horizontally by aerosol.
• Inter species transmission (species jumping)of BCoVs combined with their ability to
recombine would lead to emergence of more genetically divergent CoVs.
28. 3-Canine Respiratory Coronavirus
• In2003, anew coronavirus was identified in the respiratory tract of dogs housed in a
rehoming kennel in the United Kingdom. This virus was referred to as CRCoV.
• The genetic relationship of CRCoV to BCoV spike protein suggests that the virus was
probably transmitted to dogs from cattle.
• CRCoV is responsible for mild respiratory disease in dogs. However, in most of the Cases it
contributes to the development of canine infectious respiratory disease (CIRD) together
with other canine respiratory pathogens (e.g., Bordetella bronchiseptica, canine adenovirus
type 1 and type 2, canine parainfleunza virus, canine herpesvirus, reoviruses, and influenza
viruses).
29. 4-Equine Coronavirus
• Coronavirus-like agents have been identified by EM examination of fecal
samples from foals and adult horses having enteric disease and fever.
• Phylogenetic analysis has demonstrated that ECoV NC99 strain is most
closely related to BCoV, HCoV-OC43, and PHEV.
30. 5-Mouse Hepatitis Virus
• MHV is highly contagious and causes explosive outbreaks of disease in
mouse colonies throughout the world. The severity of the clinical disease
depends on several factors. These factors can be broadly classified into viral
(strain, dose, and route of infection) and host factors (strain ofmice, age, and
immune status).
31. 6-Rat Coronavirus
• It is a severe, self-limiting inflammatory disease of the upper respiratory
tract, salivary and lacrimal glands, and eyes of rats.
• The virus is highly contagious and causes high morbidity and low mortality
in infected colonies.
32. Animal Diseases Caused by Members of the
Genus Gammacoronavirus
• 1-Avian Infectious Bronchitis Virus Disease.
• Avian bronchitis virus (IBV) is one of the most significant causes of
economic losses within the poultry industry, affecting the performance of
both egg-laying and meat-style (broiler) birds. Avian IBV causes respiratory
disease in chicks 10 days to 4 weeks of age; however, all ages,
• sexes, and breeds are susceptible to infection although mortality is low in
birds greater than 6 weeks of age.
33. • the virus replicates not only in the upper and lower respiratory tract but also
in the alimentary tract (e.g., esophagus proventriculus, duodenum, jejunum,
cecal, tonsils, rectum, cloaca, and bursa of Fabricious) and other tissues such
as reproductive tract (e.g., oviduct and testes) and kidneys.
• Morbidity is 100% and mortality may exceed 25% in young chicks.
• the incubation period of IBV infection is 18–36 h. Virus gains entry via the
respiratory tract, and the respiratory form of IBV results in tracheitis and
bronchitis.
34. 2-Turkey Coronavirus
• TCoV is the causative agent of coronavirus enteritis (CE) of turkeys. It is an acute
and highly contagious disease of turkeys of all ages and is of major economic
importance to the turkey industry.
• Synonyms of the disease include blue comb disease, mud fever, transmissible
enteritis, and infectious enteritis. The disease affects primarily the Alimentary tract
and is characterized by depression, subnormal body temperature, anorexia,
inappetence, loss of body weight, and wet droppings. Darkening of the head and
skin and tucking of the skin over the crop are characteristics of infected growing
turkeys. A rapid drop in egg production with formation of chalky eggshells occurs
in producing breeder hens. Morbidity is essentially 100%, and mortality varies with
age and environmental conditions.
35. Animal Diseases Caused by Members of the
Genus Torovirus
• Four species of toroviruses have recently been identified:
• BToV, PToV, EToV, and HuToV.
• It has been speculated that toroviruses are associated with enteric disease in
many animal species.
• Predominantly affected are 2−3-week-old calves and they tend to have only
mild diarrhea by 3−4 months of age but continue to shed the virus.