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GIDSAS Chotani, 2003 Chotani, 2003 PART III: The Virus PART III: The Virus

GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

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Page 1: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

PART III: The VirusPART III: The Virus

Page 2: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

CoronavirusCoronavirus

Single-strand RNA, nonsegmented, Single-strand RNA, nonsegmented, enveloped, ~31,000 NTsenveloped, ~31,000 NTs

2 serogroups (229E and OC43) in humans2 serogroups (229E and OC43) in humans~1/3 of common colds~1/3 of common colds

Reinfections commonReinfections common

EnvelopeEnvelopeS - spike proteinS - spike protein

M - matrix proteinM - matrix protein

HE - hemagglutininHE - hemagglutinin

Page 3: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Coronavirus FamilyCoronavirus Family

Cause mild to moderate respiratory illnesses Cause mild to moderate respiratory illnesses such as common cold.such as common cold.

Able to survive in dry air for up to 3 hours.Able to survive in dry air for up to 3 hours.

Can be killed by exposure to ultra-violet light, so Can be killed by exposure to ultra-violet light, so they will not survive under sunlight.they will not survive under sunlight.

Mutate easily, and each mutation triggers off an Mutate easily, and each mutation triggers off an epidemic of respiratory disease.epidemic of respiratory disease.

Page 4: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Coronavirus FamilyCoronavirus Family

A new mutation, which arose in Guangdong A new mutation, which arose in Guangdong is suspected of causing SARSis suspected of causing SARS

The name “coronavirus” refers to the The name “coronavirus” refers to the protein molecules surrounding the virus, protein molecules surrounding the virus, making it look like a crown (n.“corona” making it look like a crown (n.“corona” lat lat = crown).= crown).

Page 5: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

CoronavirusesCoronaviruses

SurvivalSurvival229 E229 E

6 days in suspension6 days in suspension

3 hours after drying on surface3 hours after drying on surface

OC43OC43<<1 hr after drying on surfaces1 hr after drying on surfaces

Page 6: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Laboratory Evidence as of Laboratory Evidence as of 4/03/20034/03/2003

Culture (Vero E6 cells)Culture (Vero E6 cells)

EM (cell culture, BAL)EM (cell culture, BAL)

PCR (tissue, swabs)PCR (tissue, swabs)

Serology (IFA, EIA)Serology (IFA, EIA)

HistopathologyHistopathology

Viral growthViral growth

Virus-like Virus-like particles, particles, CoronavirusCoronavirus

Coronaviral Coronaviral nucleic acidnucleic acid

AntibodyAntibody

DAD (ARDS)DAD (ARDS)

44

22

1111

55

44

AssayAssay FindingsFindingsNo. pos. No. pos. patients*patients*

*Results not mutually exclusive*Results not mutually exclusiveSource: CDCSource: CDC

Page 7: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

Coronavirus-Coronavirus-infected Vero E6 infected Vero E6 cells (isolate from cells (isolate from SARS patient) by SARS patient) by thin section EMthin section EM

Page 8: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E
Page 9: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Vero E6 cells inoculated with Oropharyngeal Specimns from Patients with SARS.The typical early cytopathic effect seen with coronavirus isolates from patients with SARS is shown in Panel A (x40). Infected Vero cells are shown reacting with the serum of a convalescent patient in an indirect fluorescence antibody assay in Panel B (x400).

Ksiazek et al. A novel Coronavirus associated with SARS. NEJM April 10, 2003

Page 10: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Ultrastructural characteristics of SARS-Associated Coronavirus Growth in Vero E6 cells.Panel A shows a thin-section electorn-microscopical view of viral nucleocapsids aligned along the membrane of the rough endoplasmic reticulum (arrow) as particles bud into the cisternea. Enveloped virions have surface projections (arrowhead) and an electron-lucent center. Directly under the viral envelope lies a characteristic ring formed by the helical nucleocapsid, often seen in cross-section. Negative stain electron microscopy (Panel B) shows a stain-penetrated coronavirus particle with an internal helical nucleocapsid-like structure and club-shaped surface projections surrounding the periphery of the particle, a finding typical of coronaviruses (methylamine tungstate stain). The bars represent 100 nm.

Ksiazek et al. A novel Coronavirus associated with SARS. NEJM April 10, 2003

Page 11: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

Coronavirus Coronavirus particle by negative particle by negative stain EMstain EM(isolate from patient (isolate from patient with SARS)with SARS)

Page 12: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

Coronavirus-infected Coronavirus-infected cellcellin BAL of SARS patientin BAL of SARS patient

Page 13: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

Lung of patient with Lung of patient with fatal SARS showing fatal SARS showing diffuse alveolar diffuse alveolar damage and syncytial damage and syncytial giant cellsgiant cells

Page 14: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

Multinucleated syncytial giant cellsMultinucleated syncytial giant cellsin lung of SARS patientin lung of SARS patient

Page 15: GIDSAS Chotani, 2003 PART III: The Virus. GIDSAS Chotani, 2003 Coronavirus Single-strand RNA, nonsegmented, enveloped, ~31,000 NTs 2 serogroups (229E

GIDSAS

Chotani, 2003Chotani, 2003

Histopathological Evaluation of Lung Tissue from Patients with SARS.Tissue shows diffuses alveolar damage, abundant foamy macrophages, and multinucleated syncytial cells (Panel A). Higher magnification of syncytial cells show no conspicuous viral inclusions (Panel B). Panel C shows immunohistochemical staining of SARS-associated coronavirus – infected cells

Name Proposed Urbani Coronavirus

Ksiazek et al. A novel Coronavirus associated with SARS. NEJM April 10, 2003