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CORONAVIRIDAE

Crown viruses

General CharacteristicsCoronaviruses

Single-stranded, positive sense RNA viruses


Enveloped and pleomorphic

Infect a wide range of mammalian and avian species

Cause respiratory and enteric disease,


encephalomyelitis, hepatitis, serositis, and vasculitis
in domestic animals. In humans, common cold.

Pronounced tropism for epithelial cells of the


respiratory and the intestinal tract.

In general, mild or inapparent infections in adults but


severe diseases in newborn or young animals.

Stability of virus; cold temperature relatively stable;


labile at room temperature; highly photosensitive

Viruses with +ve RNA


genomes
Picornaviridae
Caliciviridae

Coronaviridae
Arteriviridae
Flaviviridae
Togaviridae

footandmouthdiseasevirus

porcineenteroviruses
felinecalicivirus
coronaviruses
equinearterivirus,PRRSV
flaviviruses(WNV)
pestiviruses(BVD)
equineencephalitisviruses

Classification and General


Characteristics

Coronaviruses have also been associated with infections


of the respiratory and enteric tracts and with central
nervous system disease in monkeys, rats, rabbits, and
other species.

Unusually large club-shaped peplomers projecting from


the envelope give the particle the appearance of a solar
corona; pleomorphic; 75-160 nm

Family Coronaviruses have been divided into four


antigenic groups (Table 1). 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.

Table 1. Antigenic Groups and Diseases


Caused by Coronaviruses
Antigenic Group
I (mammalian)

Virus
Human coronavirus 299E
Transmissible gastroenteritis
Feline infectious peritonitis

Disease

Canine coronavirus

Common cold
Gastroenteritis
Peritonitis, pneumonia virus,
meningoencephalitis,
panophthalmitis, wasting
Enteritis

II (mammalian)

Human coronavirus OC43


Mouse hepatitis virus (many
serotypes)
Bovine coronavirus
Porcine hemagglutinating
encephalomyelitis virus

Common cold
Hepatitis, encephalomyelitis,
enteritis
Gastroenteritis
Vomiting, wasting, and
encephalomyelitis

III (avian)

Infectious bronchitis virus of


chickens (3 eight serotypes)

Tracheobronchitis, nephritis

IV (avian)

Bluecomb disease virus of


turkeys

Enteritis

Coronavirus Structure

The envelope carries three glycoproteins


:
S - Spike protein: receptor binding, cell fusion, major antigen
E - Envelope protein: small, envelope-associated protein
M - Membrane protein: transmembrane - budding & envelope
formation In a few types, there is a third glycoprotein:
HE - Haemagglutinin-esterase
The genome is associated with a basic phosphoprotein, N.

Coronavirus replication. Numbers of mRNAs and locations of nonstructural (NS) proteins may vary for different cornaviruses. Virions
bind to the cell membrane and enter by membrane fusion or endocytosis. Viral genomic RNA acts as mRNA to direct the synthesis of viral
RNA-dependent RNA polymerase. This enzyme copies the viral genomic RNA to form full-length (-) strand templates. These templates are
copied to form new (+) strand genomic RNA, an overlapping series of subgenomic mRNAs, and leader RNA. All mRNAs are capped and
polyadenylated and form a nested set with common 3 ends. Each mRNA codes for a single polypeptide. The N protein binds to novel viral
RNA to form helical nucleocapsids. E1, E2, and E3 glycoproteins are produced on membrane-bound polysomes. Some coronaviruses do not
encode E3. Cornaviruses that encode E3 cause hemadsorption in infected cells. Virions are formed by budding at membranes of the Golgi
apparatus and the RER, but not at the plasma membrane. Virions are released by cell lysis or by fusion of post-Golgi, virion-containing
vesicles with the plasma membrane.

Replication

SARS

Severe Acute Respiratory


Sydrome

February 2003 Guangdong, China

Viral pneumonia, fever cough,


dyspnea, headache, and hypoxem
High case fatality

Lipsitch et al 2003, Science 300: 196

SARS Coronavirus

SARS
Where did SARS come from?

palm civet (paguma larvat

SARS diagnosis
Serology ELISA, questionable
Virology-PCR

Viruses of Veterinary
Importance

Coronaviruses

Bovine coronavirus (BCV)


Transmissible gastroenteritis (TGE)
Feline infectious peritonitis (FIP)
Infectious bronchitis disease virus
(IBDV)

Bovine Coronavirus (BCV)

Viral diarrhea- Rotaviruses are the major cause of diarrhea


in the young calf. Coronaviruses are also important. The
pathogenesis is similar between the two viruses

Disease is most commonly seen in calves at about 1 week of age,


the time when antibody in the dam's milk has fallen to a low level.
The diarrhea usually lasts for 4 or 5 days. The destruction of the
absorptive cells of the intestinal epithelium of the small intestine, and
to a lesser extent those of the large intestine, leads to the rapid loss
of water and electrolytes.

Glucose and lactate metabolism is affected; hypoglycemia, lactic


acidosis, and hypervolemia can lead to acute shock, heart failure, and
death, although coronavirus diarrhea is generally less severe than
that caused by rotaviruses. Bovine coronaviruses may cause diarrhea
in humans.

Viral causes of diarrhea in


neonates

Rotavirus
Coronavirus
BVD
Bredavirus
Calicivirus
Parvovirus
Astrovirus

Susceptability of neonates

Rotaviruses 4 to 14 days
Coronavirus 4 to 30
4days
Colostral
Antibodiesingut

Susceptibleperiod

Diagnosis

FA of fecal samples
EM

Prevention

Vaccination of pregnant
animals
Colostrum for 2 weeks

vaccines against
calf diarrhoea

Bovine Coronavirus (BCV)

Winter dysentery is a sporadic acute disease of


adult cattle that occurs in many countries
throughout the world, and it is believed to be
caused by coronaviruses.

The clinical syndrome is characterized by bloody diarrhea


accompanied by decreased milk production, depression,
and anorexia.

Available vaccines are not effective, because they do not


appear to contain sufficient antigenic mass and cannot be
given early enough. Alternatives to vaccinating calves are
to immunize the dam to promote elevated antibody levels
in the colostrum or to feed antibody directly to the calf in
colostrum.

Transmissible Gastroenteritis Virus (TGE

Transmissible Gastroenteritis Virus


(TGEV)

TGEV of swine usually occurs in the winter


months

Characterized by an explosive outbreak of


vomiting and profuse diarrhea

Transmissible gastroenteritis is one of the


major causes of death in young piglets in the a
midwestern United States. Mortality is high,
vaccines are of limited efficacy, and it appears
to be difficult to prevent the introduction of the
virus into herds.

Transmissible Gastroenteritis Virus


(TGEV)
Clinical Features
The disease is usually recognized at farrowing time.

The incubation period is usually 1-3 days, and all litters within the
farrowing house are commonly affected at the same time.
The clinical signs in piglets are vomiting followed by a watery
diarrhea and rapid loss of weight. The diarrhea is profuse, with an
offensive odor, and often contains curds of undigested milk.
Piglets infected when under 7 days of age generally die within 2 to 7
days of the onset of signs; piglets over 3 weeks of age usually live
(may be unthrifty for several weeks). In growing, finishing, and adult
swine the disease is commonly associated with inappetence and
diarrhea of a few days' duration, and may even go unnoticed. Sows
infected late in pregnancy may develop pyrexia, but they are
otherwise normal and rarely abort.

TGE IHC: Immunocytochemistry Infected Epithethial Cells

Transmissible Gastroenteritis Virus


(TGEV)
Diagnosis
presumptive diagnosis of TGE can be made from
the sudden appearance of a rapidly spreading and
often fatal disease of young piglets accompanied by
vomiting and diarrhea.

clinical diagnosis can be confirmed by


demonstration of specific antigen by
immunofluorescence, isolation of virus, and
demonstration of rising antibody titers in paired

sera.

Transmissible Gastroenteritis Virus


(TGEV)
Epidemiology and Control
Transmissible gastroenteritis occurs most commonly in the
winter months (in North America between November and
April), but its source is unknown. Its presence becomes
apparent only when large numbers of piglets are born at a
time when weather conditions favor transmission.
Control is difficult, although good management of the
farrowing house can reduce the risk. The most widely used
vaccination regimen involves vaccinating the sow with an
attenuated vaccine 3 weeks before farrowing, thus
providing piglets with high levels of protective antibody in
the colostrum during the critical first few days of life.

feline infectious peritonitis


HorzinekandH.Lutz
AnupdateonFIP
VeterinarySienceTomorrow
Jan,2001
www.vetscite.org

FIP

fatal disease of young cats (3-18 mo)


in multi-cat houses or catteries
not seen before 1950

new virus?
old virus, new disease

systemic antibodies not protective,


may even be harmful (antibody
dependent enhancement, early
death)

feline enteric coronavirus

closely related to dog, pig (TGE),


human coronaviruses

species specific but K9CV can infect


cats

two serotypes

serotype I

more common, 70-95% of isolates, does not


cross react with K9CV
difficult to isolate

FeCV, serotype 2

BothserotypescanleadtoFIPcausingstrains

FeCV

very prone to making mistakes during


replication

1/10,000 nucleotides
quasispecies
invariant portion of genome

primers for RT-PCR

mild enteric or respiratory disease


grows mainly in epithelial cells
persistent infections

in balance with immune system


low levels of antibody

FIPvirus

derived by mutation from FeCV


nature of mutation not defined
few obvious common mutations in
FIP causing strains
No reliable technique for
differentiating between nonvirulent and virulent strains
not usually spread from cat to cat

epidemiology

Exposure to FeCV

25% of cats from 1-2 cat households are


seropositive
75-100% of cats from catteries seropositive

susceptible cats become infected immediately


following exposure
kittens can become infected in utero or soon after
maternal antibodies drop below protective levels

epidemiology (FIP)

1:5,000 in 1-2 cat households


1:20 in catteries

sporadic
clustered9 (2-3 cats)
rarely epidemic - 40% mortality

no gender or breed predisposition

persistent infections

cats can shed virus (RT-PCR of blood and


feces) for long time
persistence not reinfection
virus replicates in a few epithelial and
lymphoid cells

immunohistochemistry

each cat has own collection of viruses


protected from infection by other strains

premunition
reason for rare horizontal transmission of FIP

FIP
pathogenesis
FEC
Milddiarrhoea
orrespiratoryillness
virus

immune system
persistentinfection

lowlevelofreplicationinepithelialandlymphoidcells

pregnancy in
young queens
weaning, sale,
shipment,
adaptation

elective surgery
concurrent infections
(FeLV, FIV ?)

Virus

immune
system

increasedvirusreplication>virulentmutants
increasedabilitytogrowinmacrophages
immunemediatedlysisofinfectedcells
cytokinesdrawinmoresusceptiblecells
vascularpermeability
immunecomplexrelateddamage

clinical signs

common signs

chronic antibiotic unresponsive fever


progressive anorexia, weight loss
stunting of growth
progressive increase in serum proteins
increase in globulins
anemia
serum, urine brown due to bilirubin

clinical signs

wet form

peritonitis
pleuritis

dry form

surface oriented granulomas

mesenteric lymph nodes, liver, kidneys, cecum


(palpable)
cloudiness in eye
neurological signs

can change from dry to wet

diagnosis

serology

prognosis?

no titer - no FIP but may still be infected


<100 - less chance of developing FIP
>100 - greater chance of getting FIP

increased globulins and protein (>35g/L)


cytology

degenerate and non-degenerate PMN,


macrophages, some lymphocytes, protein
background
FeCV positive cells (FAT)

diagnostic alogrithm
(Horzinek and Lutz)

diagnostic algorithm

diagnostic algorithm

control

vaccine

Primucell FIP

Intranasal ts virus

management

early weaning and separation

Viruses of Veterinary Importance


Avian Infectious Bronchitis Virus (IBV)

Avian infectious bronchitis (gasping disease) is one


of the most important viral diseases of chickens.
IBV is responsible for an acute respiratory disease
which can produce very high mortality rates in
young chicks.

Viruses of Veterinary Importance


Avian Infectious Bronchitis Virus (IBV)
Clinical Features
Outbreaks of infectious bronchitis are explosive. IBV
spreads rapidly to involve the entire flock within a few
days.

Chicks between 1 and 4 weeks of age show the most


severe disease, which is recognized initially by coughing,
sneezing, nasal discharge, and respiratory distress.
Mortality in young chicks is usually 25-30% but in some
outbreaks can be as high as 75%.

In older birds the disease often goes unnoticed, but in


laying hens there is a marked drop in egg production, with
many soft-shelled and malformed eggs being laid.

Viruses of Veterinary Importance


Avian Infectious Bronchitis Virus (IBV)
Pathology and Pathogenesis
The course of the disease in young chicks is from 7 to 21 days
depending on the severity of the disease. Necropsy of young
chicks dying from infectious bronchitis shows sinuosities,
catarrhal tracheotis, bronchitis, and congestion and edema of
the lungs. Caseous plugs may be present in the bronchi.

The primary target for viral replication is the trachea, but the virus
also replicates in the lungs, ovaries, and lymphoid tissue.

IBV can establish persistent infection in some chickens, which


results in shedding of virus in the feces for several months after
initial exposure to the virus. When virus persists in the presence of
high levels of antibody, severe nephritis can occur, which possibly
reflects an immune complex-mediated disease.

Viruses of Veterinary Importance


Avian Infectious Bronchitis Virus (IBV)
Laboratory Diagnosis
In contrast to several of the coronaviruses, IBV can be
easily isolated by the allantoic inoculation of 9- to 12day-old embryonated eggs obtained from
seronegative hens. Infected embryos are to a variable
degree stunted or curled tightly. A range of cell and
organ cultures can also be used for virus isolation.
At least eight genotypes of IBV exist and fall into two
major groups; virus isolates of widely differing
pathogenicity occur within each antigenic group.

Avian Infectious Bronchitis Virus (IBV)


Epidemiology and Control
IBV spreads between birds by aerosol and by ingestion of food
contaminated with feces. Control of infectious bronchitis is
difficult because of the presence of persistently infected chickens
in many flocks.

Outbreaks of infectious bronchitis have declined in recent years through


use of vaccines; however, it may occur even in vaccinated flocks following
the introduction of infected replacement chicks from another farm. To
minimize this risk, most poultry farms purchase only 1-day-old chicks and
rear them in isolation.
Attenuated vaccines, administered in the drinking water or as aerosols,
are widely used to protect chicks and are usually given between 7 and 10
days, and again at 4 weeks. Vaccination earlier than 7 days may be
unsuccessful because most chicks have passive immunity up to this age.
Local immunity in the respiratory system is critical for protection and can
be generated by heterotypic vaccine strains.

Avian infectious bronchitis. (A) One synonym for the disease is gasping disease. (B) Thick
mucopurulent exudate in the trachea. (C) Nephrosis. The kidney is pale and enlarged to about five
times normal size. (D) Embryos from embryonated hens eggs inoculated via the allantoic cavity
with serial dilutions of virus when 9 days old, and examined 11 days later. Amounts of virus
diminish in pairs from right to left in the top row, and from left to right in the bottom row.

Other coronaviruses of
importance in veterinary
medicine
Porcine respiratory coronavirus (PRCV)

Porcine Hemagglutinating
Encephalomyelitis virus
Porcine epidemic diarrhea virus (PEDV)
Canine coronavirus (CCV)
Turkey coronavirus (Bluecomb disease
of turkeys)
Mouse Hepatitis Virus