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 isolate in cell culture are difficult to 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

replication which is unusual for virus with unsegmented genome during an RNA

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

and Avian CoV only Turkey

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 III NO HUMAN strains SARS CoV gp II (OC43)

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 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 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 infected is

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

Name

2.Envelope

3.Structur

e DNA Adeno Not Enveloped 70-90 nm ds-DNA non segmented icosahedral Rhino Not Enveloped , 20-30nm Ss +vesense Non segmented Icosahedral symmetry < 100 serotypes 4. Antigenic structure 5.Tropism

6.Spread

six groups (A to F) 49 types Adenoviruses infect and replicate in the epithelial cells Spread To Regional Lymph Nodes EXCEPT in the immunocompromised Cells URT Do Not Spread RNA viruses Orthomyxo Corona Enveloped 80-120 nm ss –ve Sense segmented RNA Helical symmetry A,B,C 15 H, 9N Respiratory mm Do Not Spread Enveloped 80 to 160 nm ss+ve RNA non segmented Helical symmetry 4 groups RT GI 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 8.Treatment

No antiviral drug No antiviral Treatment SARS Vero monkey cells No successful treatment 9. Important feature Latency oncogenic potential in animals 10. VACCINE < 50% of URTI Mutability & high frequency of genetic reassortment Available high frequency of: deletion mutations high frequency of recombination during replication -

4 families of 1ry Respiratory viruses

DNA RNA viruses Adeno Rhino Orthomyx o 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