Neel K.

Krishna
Associate Professor
Microbiology & Molecular Cell Biology
Pediatrics
KrishnNK@EVMS.EDU
LH 3184, x5677

Research Experience:
Molecular Virology, Complement Biology,
Complement Drug Development

Caliciviruses

Identify and describe

The viral pathogens most
closely associated with
gastroenteritis
The structure and
replication of
caliciviruses/norovirus
The transmission,
epidemiology, clinical
course, diagnosis and
preventive measures for
caliciviruses/norovirus

Calicivirus

What characteristics of this

viral family make it so
infectious?
What is the clinical
implication of
asymptomatic viral
shedding?
Why is there no vaccine for

Viral pathogens
causing gastroenteritis
Proven causes Uncertain role
Caliciviruses Picornaviruses (Aichi virus)
Astroviruses Picobirnaviruses
Reoviruses (rotavirus) Toroviruses
Enteric adenovirus Coronaviruses
Others

Major health issues

resulting from viral
gastroenteritis

Dehydrating diarrhea and metabolic

acidosis (can lead to death)
Outbreaks of illness in hospitals,
child care centers, and nursing
homes
Contaminated water and food
supplies, leading to closing of
restaurants and hotels and/or
withdrawal of prepared foods and/or

Impact of Gastroenteritis: Annual

Estimates for Children < 5 Years
of Age
USA

Outcome
Diarrhea

World

35 million episodes 0.5 - 1 billion*

Physician visits

2 3.7 million

Hospitalizations

>200,000

45 90 million

~500

3 3.5 million**

Deaths

* ~ 5 to 6 episodes per child per year

** > 1400/day
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Key concepts to remember

about enteric viruses
Enteritis viruses
Some viruses are recognized from the disease
they cause by infection of the intestine. These
viruses are the gastroenteritis viruses. The bestknown example is rotavirus, a common cause of
diarrhea and vomiting in children.
Enteric viruses with extraintestinal manifestations
Other viruses are recognized from the disease
they cause outside the intestine. The classic
example is poliovirus that, although causing first
an intestinal infection often with no or very mild
symptoms, usually comes to medical attention
only after infecting nerves.
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Key concepts to remember

about enteric viruses
(continued)
Common Syndrome

Multiple pathogens, among them multiple

viruses, cause gastrointestinal illness. The
features of illness from their enteric pathology
are in common, much like the multiple
pathogens that cause the syndrome of
pneumonia. For gastroenteritis pathogens, the
common features of illness are diarrhea,
vomiting and fever, with variable amounts of
intestinal cramps, malaise, and loss of appetite.
Birds of a Feather
The presence of one enteric pathogen markedly
increases the likelihood that two or more are

Caliciviruses
Small, non-enveloped, (+)
strand RNA viruses with
icosahedral symmetry.
Characteristic cuplike
depression on surface of virion
that are readily visualized by
electron microscopy.
Acid stable and resistant to
the low pH encountered in the
stomach.
Not able to be efficiently
propagated in tissue culture
and therefore our knowledge
of the replicative cycle of this
virus is limited.

Calicivirus
Replication

Key
concepts
Caliciviruses
are small, non-

enveloped, (+) strand RNA

viruses with icosahedral
symmetry.
Positive-strand (+) RNA viruses
have single-stranded RNA
genomes of the same polarity as
mRNA.
The (+) strand RNA virus genome
functions as mRNA and the naked
RNA is infectious.
All (+) RNA viruses encode an
RNA-dependent RNA polymerase
(RdRp) for genome replication.

(+) RNA viruses do not carry the

RdRp as part of the virion.

Li D et al. Microbiol. Mol. Biol. Rev.

2013;77:253-266
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Calicivirus
Replication

Glass, Parashar and Estes, N Engl J

Med, 2009

After replication, a subgenomic mRNA fragment is produced that codes for

the structural (capsid) proteins.
This separates virus replication into two phases: early (nonstructural proteins
to replicate the viral genome) and late (structural proteins to assemble the
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virion).

Caliciviruses
Medically relevant
caliciviruses
are divided into two genera:

Norovirus
type species: norovirus (Norwalk-like
viruses)
Number of strains > 52 (2009)
Sapovirus
type species: Sapporo-like virus
Number of strains > 6 (2002)

Noroviruses are the

prototypical caliciviruses

Norovirus Clinical Manifestations

Noroviruses cause acute
gastroenteritis in children and
adults, characterized by acute
onset of vomiting, diarrhea,
nausea, abdominal cramps and
Symptoms are indistinguishable
fever.
from those associated with
rotavirus, astrovirus or with
bacterial or parasitic agents.
Norovirus incubation is short
(mean, 24 hours) and duration
of illness is 1-2 days.
Diarrhea is generally watery
without blood or mucus.

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orovirus Transmission/Epidemiolog
Norwalk virus is named for an outbreak of
gastroenteritis in a school in Norwalk, Ohio (1969).
Transmitted horizontally by the fecal-oral route.
The most common cause of gastroenteritis
outbreaks among adults in the US and cause an
estimated 23 million cases annually.
Have a worldwide distribution and affect all age
groups, whereas acute gastroenteritis caused by
astrovirus and rotavirus is a disease of infants and
young children.
As
few as 10 viral particles will initiate disease in
humans.
Up to 100 billion virions are released per gram of
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feces!

orovirus Transmission/Epidemiolog
Outbreaks have occurred in schools, camps, cruise
ships, restaurants and families.
While noroviruses have gained notoriety for
causing outbreaks of acute gastroenteritis on
cruise ships, 60-80% of all such outbreaks occur
on land.
Outbreaks are associated with the ingestion of
contaminated food or water, direct person-toperson contact and contact with contaminated
environmental surfaces (fomites).
Noroviruses have no seasonal incidence.

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rovirus Pathogenesis and Virulence Facto

Infects the small bowel and directly damages enterocytes.
Binds to and utilizes histo-blood group (ABO) antigens as
receptors on the cell surface.

Intestinal microvilli are broadened and blunted as damaged

enterocytes slough off.

Norovirus-induced pathology leads to transient malabsorption of

water and nutrients and reduced gastric motility, culminating in
vomiting and diarrhea. Many asymptomatic infections occur as
well.

Shedding of virus may continue up to two weeks after symptoms

disappear. Up to 30% of individuals are asymptomatic but can
spread the infection.
Norovirus antibody is detected after infection and confers
short-term protection, but knowledge of the role of immunity
in norovirus infection is incomplete.

No virulence factors have been identified.

Laboratory Diagnosis
RT-PCR assays have been developed to detect norovirus in
stools and other clinical or environmental samples.
ELISAs are also available to detect virus, viral antigens or
norovirus-specific antibody in serum. Serology can be used to
confirm the diagnosis.
ImmunoEM can be used to concentrate and identify virus from
the stool.
In reality, laboratory diagnosis is not routinely performed
unless there is a significant outbreak or for epidemiological
purposes.

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Norovirus Treatment and

Prevention
There is no specific antiviral therapy.
No vaccine is available to prevent
norovirus infection.
Frequent hand washing is an effective
means of prevention and disposal of
contaminated food and disinfection of
contaminated materials will prevent
transmission.

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