Coronaviruses

Chapter 40

Structure and Composition

Enveloped
Spike proteins resemble solar corona

or crown
120-160 nm
Positive-strand RNA (27-32 kb)
Cytoplasmic replication
Budding into ER and Golgi
Notoriously difficult to propagate in
culture
High frequency of recombination
Cause colds and severe acute
respiratory syndrome (SARS)

Classification
Family Coronaviridae
Genus Coronavirus
Genus Torovirus
Replication
Details are largely unknown because viruses are difficult to

grow in cell culture

Mouse hepatitis virus is model for coronavirus replication

Viral spike proteins mediate attachment

Aminopeptidase N is a cell receptor target for many coronaviruses

Endocytosis is thought to mediate infection

After uncoating, the viral genome (mRNA) is translated to produce RNA
polymerase
Subgenomic RNAs are synthesized for each viral polypeptide
Genomic RNA is cosynthesized with nucleocapsid

Results in nucleocapsid binding immediately to genomic RNA

Progeny virus buds from ER and Golgi and are packaged into vesicles
Vesicles travel to and fuse with plasma membrane, releasing viral particles
from cell

Coronavirus Infections

Pathogenesis
Limited knowledge
Highly species-specific
Typically mild upper respiratory infections (colds) that

remain localized
Exception: SARS
Immunity is not durable
Many people become resusceptible after a few years
Laboratory Diagnosis
ELISA - may not discriminate past infections
HA
PCR
Virus isolation is difficult (often impossible) and requires
great expertise

Severe Acute Respiratory

Syndrome

Initial outbreak in SE Asia

Hong Kong and Singapore first reported
Disease originated in China
Originally thought to be from wild game markets

Palm civet cat (which isnt a cat) - Paradoxurus

hermaphroditus
Raccoon dog (which isnt a dog) - Nyctereutes
procyonoides

It is a bat virus
Chinese horseshoe bats (Rhinolophus sinicus)
No virus isolation

Amplification of coronavirus RNA from anal swabs

Serology
It is highly-similar, but not identical to SARS-CoV

Mutations have most likely occurred in transmission

from bats to civets to humans
Reverse genetics of SARS-CoV and some bat
viruses has been done

No animal pathogenesis model

SARS CoV

Coronavirus Phylogeny

Chymotrypsin-like protease (3CLpro), RNA-dependent RNA

polymerase (Pol), spike (S), and nucleocapsid (N)

Coronaviruses Are Bat

Viruses

SARS Pathogenesis

Virus is transmitted by respiratory and fecal routes

Infection is mediated by human angiotensin-converting
enzyme 2 (hACE2) receptor
High expression
Lung alveolar epithelial cells
Intestinal enterocytes
Low expression
Blood vessels (virtually all organs)
Pneumonia
Cause of death is lung failure

Pulmonary Inflammation of SARS

Pathologic findings of lung tissue sections. A: Pulmonary congestion and edema (H&E stain,
original magnification x100). B: A mild degree of interstitial lymphocytic infiltration. Intraalveolar organizing exudative lesion was occasionally found. Detached atypical pneumocytes
indicated by arrow (H&E stain, original magnification x200). C: Atypical multinucleated
pneumocytes were occasionally identified. Definite viral inclusion was not apparent (H&E
stain, original magnification x400). D: Fibrin thrombi were frequently noted in small pulmonary
arteries and arterioles (H&E stain, original magnification x200).

Is SARS an
Immunopathogenesis?
Criterion

Evidence in SARS

Precedent in other viral infections

Controversial; viral titres,

measured in nasopharyngeal- MHV-induced demyelination increases as virus is
aspirate samples, decrease as cleared; MHV-3-induced hepatitis correlates with
Worse disease with
clinical disease worsens; but
macrophage activation and not viral load; and
decrease in viral load
high viral loads have been
IBV-induced nephritis is detected in chickens
detected in lungs and immune
with very low viral loads
cells after death
Macrophage or DC
infection

Infection is abortive but induces

expression of pro-inflammatory MHV and FIPV productively infect macrophages
mediators

In MHV infection, macrophages infiltrate the CNS

Macrophage
coincident with demyelination (thought to be the
Macrophages are present in
infiltration into sites
final effector cell); and in FIPV infection,
large numbers in infected lungs
of inflammation
macrophages are the main cell type in
granulomas and are crucial for pathogenesis
High concentration
Controversial; antiof pro-inflammatory inflammatory mediators might
mediators in serum
contribute to delayed viral
or at site of infection
clearance
Inhibition of type I
IFN induction in
infected cells

Shown using isolated

macrophages, DCs and
fibroblasts

Lymphopenia and
neutrophilia

Present in most severe cases;

and lymphocytic infection has
been detected

MHV-3-induced FGL2 expression is crucial for

liver necrosis; in MHV-JHM-infected mice, IFN- is
required for CD8+ T-cell-mediated responses;
and in FIPV infection, increased cytokine
concentrations are present in blood and tissues
during exacerbation of disease
MHV does not induce type I IFN expression
In FIPV infection, lymphopaenia is present during
clinical relapses; and in MHV-3 infection,
lymphopaenia is present and lymphocytic