CORONAVIRUSES

CORONAVIRUSES
Genus Coronavirus
CoV
&
Genus Torovirus
Coronaviridae
 CORONAVIRUSES
The 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

Genus Coronaviruses are difficult to

isolate in cell culture

So infections with this virus are

rarely diagnosed in clinical practice
 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 strains
a 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 I
(229E)

gp II
(OC43)
gp III
SARS CoV
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
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 by
Immunofluorescent 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 coronaviruses
EXCEPT:
• 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 Measures
1. Isolation of patients

2. Quarantine of those exposed

3. Use of barrier Precautions:

1. gloves
2. gowns
&
3. respirators by health workers

1. 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.NA DNA RNA viruses

Name Adeno Rhino Orthomyxo Corona

2.Envelope
Not Not Enveloped
Enveloped Enveloped
Enveloped
3.Structure 70-90 nm , 20-30nm 80-120 nm 80 to 160 nm
ds-DNA Ss +vesense ss –ve Sense ss+ve RNA
segmented RNA
non segmented Non segmented non segmented
Helical symmetry
icosahedral Icosahedral Helical symmetry
symmetry
4. Antigenic six groups (A to F) <100 serotypes A,B,C 4 groups
structure 49 types 15 H, 9N

5.Tropism Adenoviruses infect and Cells URT Respiratory mm RT

replicate in the epithelial
GI
cells

6.Spread Spread To Regional Do Not Spread Do Not Spread Do Not Spread

Lymph Nodes EXCEPT
in the
immunocompromised
 4 families of 1ry Respiratory viruses
DNA RNA viruses
Adeno Rhino Orthomyxo Corona
7. Isolation Human cells are Cells of primate Primary tissue human embryonic
required origin, culture MK tracheal organ
cultures
Human diploid
fibroblast cells SARS Vero
monkey cells

8.Treatment No antiviral drugNo antiviral Treatment No successful

treatment

9. Important Latency < 50% of URTI Mutability & high high frequency of:
oncogenic potential frequency of genetic deletion mutations
feature reassortment
in animals high frequency of
recombination during
replication

10. VACCINE
- Available -
-
 4 families of 1ry Respiratory viruses
DNA RNA viruses
Adeno Rhino Orthomyxo Corona
11. THREAT Epidemic & Potential
LATENCY No potential repetition of
pandemics infections similar
Threat to SARS

50% Seasonal URT 15%

12. Infections A. Respiratory diseases 5%:
B. Eye infections:
C. Gastrointestinal disease:
& to 30%
D. OTHER DISEASES:
of
- Acute haemorrhagic cystitis
epidemic Diarreaha
Immuno-compromised
URT
patients manifestations are:
influenza SARS
-Pneumonia
-hepatitis
-gastroenteritis