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