coronavirusescoronaviruses genus coronavirus cov& genus torovirus
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CORONAVIRUSESCORONAVIRUSESCORONAVIRUSESCORONAVIRUSES
Genus CoronavirusGenus Coronavirus
CoVCoV
&&
Genus TorovirusGenus Torovirus
Coronaviridae
CORONAVIRUSESThe genome
- SS linear non segmented +ve sense RNA
- the largest among RNA viruses.
The family coronaviridae is composed of two genera:
• Genus Coronaviruses
• Genus Torovirus:– widespread in horses & cattle – associated with gastroenteritis.
Genus Coronavirus• First isolated in chicken in
1937
• First human corona virus was isolated in 1965
• They cause prevalent disease in humans and domestic animals (cats, dogs, birds…)
Structure:
• Coronaviruses are large enveloped virions 80 to 160 nm,
• Helical nucleocapsids.
A Crown-like Appearance when
viewed by EM
•On the surface of the envelop are club shaped projections that
resemble a solar corona
Genus Coronaviruses are difficult to isolate in cell culture
So infections with this virus are rarely diagnosed in clinical practice
Genus Coronaviruses
Tropism To Epithelial Cells
• Respiratory tract
• GI in infants
Relationship to human infections
- Based on serologic studies, coronaviruses cause respiratory tract infections and pneumonia in humans.
- Electron microscopy links coronaviruses to gastroenteritis in infants children and adults ( tropism to epithelial cells)
Genetic variation & evolution of new
strainsa high frequency of: • deletion mutations
• high frequency of recombination during replication which is unusual for an RNA virus with unsegmented genome
The three major antigenic groups of
CoV• Group I contains canine, feline,
porcine coronaviruses and a human corona virus HCoV 229E the prototype of the group
• Group II contains bovine, porcine, rat and mouse CoV and the other human strain which is OC43
• Group III no human strains only Turkey and Avian CoV
Evolution of SARS 2002
• A novel human corona virus named SARS associated corona virus represents a new fourth antigenic group intermediate between groups I & III
A NOVEL FOURTH ANTIGENIC GROUP
SARS
Evolution of SARS
gp IIISARS CoV
gp II (OC43)
gp I gp I (229E)(229E)
NO HUMAN strains
Clinical picture & epidemiology
• Upper respiratory infections, similar to “colds” caused by rhinoviruses, but with a longer incubation period (average three days).
– 15-30% of respiratory illness in adults during winter months but lower respiratory infections were rare.
– Antibodies appear early in childhood and are found in 90% in adults
CLINICAL PICTURE & EPIDEMIOLOGY
• CORONAVIRUSES may be associated with gastroenteritis which occurs year-round.
• Confirmation of the etiology of this relationship is needed.
Laboratory Diagnosis
•Direct Detection
• Isolation
•Serology
Laboratory Diagnosis of 1. coronaviruses
DIRECT DETECTION:• Antigen detection in cells of respiratory
secretions by IF or ELISA
• NA detection in respiratory secretions by RT-PCR
ISOLATION:• CoV are difficult to grow in CC.
• Reliable isolation of the virus is accomplished using human embryonic tracheal organ cultures.
• These methods are not routinely available.
Detection of Corona virus byImmunofluorescent
Technique
Serology:
• Serologic tests are not routinely available.
Practical means to confirm coronavirus infection using paired sera to detect rising or stationary high antibody level by:
- PASSIVE HAEMAGGLUTINATION TEST
- ELISA
Laboratory diagnosis of Gastroenteritis caused by
toroviruses
BASED ON DIRECT DETECTION ONLY:
• Ag detection
• NA detection
SARS
SEVERE ACUTE RESPIRATORY SYNDROME
SARS
• Mystery pneumonia late 2002 in southern China
• Resulting in progressive respiratory failure
SEVERE ACUTE RESPIRATORY SYNDROME
• Animal strain from a cat like mammal in Southern China
• Person to person spread by close contact through respiratory droplets
STRUCTURE &
CHARACTERISTICS
• Similar to coronavirusesEXCEPT:• Grown easily on tissue culture
cells resulting in cytopathic effect
• Has tropism to LRT
SARS
First coronavirus that causes severe LRT disease in humans
Clinical picture• IP: 6 days
• First epidemic 10% MR from progressive respiratory failure
Laboratory Diagnosis
• Direct Detection: NA detection
• Isolation of the virus using Vero monkey cells resulting in CPE. Confirmation by RT-PCR
• Serology: 4 fold or greater rise in antibody response by ELISA or IF
Treatment• No successful treatment
• No vaccine
YET STOPPING THE SPREAD OF INFECTION
WAS POSSIBLE THROUGH
EFFECTIVE CONTROL MEASURES
Control Measures1. Isolation of patients
2. Quarantine of those exposed
3. Use of barrier Precautions:1. gloves 2. gowns
&3. respirators by health workers
4. Hand Hygiene
Co- evolution &
pathogenicity
Majority of corona viruses cause
asymptomatic infection in their natural hosts reflecting
CO- EVOLUTION of
HOST AND PATHOGEN
WHY SARS INFCTION IN HUMANS IS
Fulminant
This is attributed to
“SARS jumped from animals to human”
i.e. A non natural host is infected
OTHER CAUSES OF FULMINANT INFECTION
• The natural host is infected by an unusual route
• The infection is caused by a more virulent virus variant
EVIDENCE OF THE EFFECT OF CO-EVOLUTION
• Milder cases of SARS Coronavirus infections in South China
• SARS coronavirus cause milder infections in populations previously affected by outbreaks
NOTE!!!
Co-evolution takes years to develop
Always remember
CHANGE IN PATHOGENICITY IS ATTRIBUTED TO
• A non natural host is infected
• The natural host is infected by an unusual route
• The infection is caused by a more virulent virus variant
4 families of 1ry Respiratory
1.NAName
DNA RNA viruses
Adeno Rhino Orthomyxo
Corona
2.Envelope Not
Enveloped
Not EnvelopedEnveloped Enveloped
3.Structure
70-90 nm ds-DNA non segmented icosahedral
, 20-30nmSs +vesense Non segmentedIcosahedral symmetry
80-120 nm
ss –ve Sense segmented RNA Helical symmetry
80 to 160 nmss+ve RNAnon segmentedHelical symmetry
4. Antigenic structure
six groups (A to F)49 types
<100 serotypes
A,B,C 15 H, 9N
4 groups
5.Tropism
Adenoviruses infect and replicate in the epithelial cells
Cells URT Respiratory mm
RTGI
6.Spread
Spread To Regional Lymph Nodes EXCEPT in the immunocompromised
Do Not Spread
Do Not Spread
Do Not Spread
4 families of 1ry Respiratory viruses
DNA RNA viruses
Adeno Rhino Orthomyxo
Corona
7. Isolation Human cells are required
Cells of primate origin, Human diploid fibroblast cells
Primary tissue culture MK
human embryonic tracheal organ cultures
SARS Vero monkey cells
8.Treatment
No antiviral drug
No antiviral Treatment No successful treatment
9. Important feature
Latencyoncogenic potential in animals
< 50% of URTI
Mutability & high frequency of genetic reassortment
high frequency of: deletion mutationshigh frequency of recombination during replication
10. VACCINE
- - Availab
le-
4 families of 1ry Respiratory viruses
DNA RNA viruses
Adeno Rhino
Orthomyxo
Corona
11. THREAT LATENCY No
Threat
Epidemic & potential pandemics
Potential repetition of infections similar to SARS
12. Infections
A. Respiratory diseases 5%:B. Eye infections:C. Gastrointestinal disease:D. OTHER DISEASES:- Acute haemorrhagic cystitis
Immuno-compromised patients manifestations are: -Pneumonia-hepatitis -gastroenteritis
50% of URT
Seasonal & epidemic influenza
URT 15% to 30%Diarreaha
SARS