VIRAL AGENTS

CAUSING
GASTROENTERITIS

Dr N. Narayan
VIRAL AGENTS CAUSING
GASTROENTERITIS
1. Rotavirus
2. Enteric adenoviruses
3. Calicivirus
4. Astrovirus
ROTAVIRUS

Family Reoviridae

Genus Rotavirus
 ROTAVIRUS
First isolated in 1973 from children with
diarrhea
EM identification from duodenal
biopsies
Human and animal strains
Rotavirus
Rotavirus- EM Structure
 ROTAVIRUS

60-80nm in size
Non-enveloped virus
Double capsid
EM appearance of a wheel with radiating
spokes
Icosahedral symmetry
double stranded (ds) RNA in 11 segments
 STRUCTURE
Double capsid (outer and inner capsid)
Core with genome

Capsid is cleaved by trypsin to form

ISVP- infective sub-viral particle

ROTAVIRUS- 3D STRUCTURE
ROTAVIRUS- ultrastructure
Rotavirus- details of EM structure
Viral Structural Proteins (VP)

Outer structural proteins - VP7 and VP4

VP7=glycoprotein

VP4=protease-cleaved, P protein, viral hemagglutinin,

and forms spikes from the surface

Inner core structural proteins VP 1, 2, 3, 6

VP6 is an important antigenic determinant

STRUCTURE
 Classification
Groups, subgoups, serotypes based on viral capsid
proteins

7 Groups (A through G)

Group A is the most common and has 2 subgroups

10 human serotypes based on G protein (VP 7)

8 P protein serotypes
 Classification (contd.)

Electropherotypes

mobility of RNA segments by PAGE

Used in epidemiologic studies

 Rotavirus - Properties
Virus is stable in the environment
Relatively resistant to handwashing
agents
Susceptible to disinfection with 95%
ethanol, Lysol, formalin
 Pathogenesis

Targeted host cells- mature enterocytes

lining the tips of intestinal villi
Intermediate/infective sub-viral particle
(ISVP) produced through proteolysis
Enter host cell by endocytosis
Virus replicates in the host cell cytoplasm
 Replication
mRNA transcription with viral RNA polymerase
Capsid proteins formed
mRNA segments formed, assembled into
immature capsid
mRNA replicated to form double stranded RNA
genome
 Histopathology

Mature enterocytes lining the tips of

intestinal villi are affected

Villous atrophy and blunting

Death of the mature enterocytes

 Histopathology

Infiltration of lamina propria with

mononuclear cells

Repopulation of the villous tips with

immature secretory cells [crypt
hyperplasia]
Histopathology
 Epidemiology - Worldwide
Millions are affected

600,000-850,000 deaths/year

A major cause of diarrhea-associated

hospitalizations

Seroprevalence studies show that antibody is

present in most by age 3y.
 Rotavirus-
Worldwide distribution
(source- centers for disease control and prevention)
 Epidemiology : U.S.
No. of children under 5y. affected ~ 2.7 million
Physician visits per year ~ 500,000
Hospitalizations per year ~ 50,000
Deaths per year ~ 20 - 40
% cases w/ dehydration ~ 1-2.5%
 Epidemiology
Age- 4mo - 2 years
Protection of younger infants through through
transplacental antibody transfer

Asymptomatic infections are common,

especially in adults

Nosocomial infections
Outbreaks
 Epidemiology (contd.)

Seasonality
Winter months (Nov. through May in US)
Gradual spread W to E
Year-round in the tropics

Incubation period - thought to be <4 days

 Epidemiology : U.S.
(Source- centers for disease control and prevention)
 Spread in the U.S.
(Source- centers for disease control and prevention)
 Epidemiology (transmission)
Mainly person to person via fecal-oral route
Fomites
Food and water-borne spread is possible
Spread via respiratory route is speculated
 Epidemiology (spread)
Contagious from before onset of diarrhea to a
few days after end of diarrhea
Large amounts of viral particles are shed in
diarrheal stools
Infective dose is only 10-100 pfu
 EPIDEMIOLOGY
Differences in Groups

Group A infections are most common

Group B has been associated with
outbreaks in adults in China
Group C is responsible for sporadic cases
of diarrhea in infants around the world
 Clinical Features
Incubation period - thought to be <4 days
Fever- can be high grade (>102F in 30%)
Vomiting, nausea precede diarrhea
Diarrhea
- usually watery (no blood or leukocytes)
- lasts 3-9 days
- longer in malnourished and immune deficient indiv.
- NEC and hemorrhagic GE seen in neonates
 Mechanism of diarrhea
Watery diarrhea due to net secretion of
intestinal fluid

Activation of the enteric nervous system -

possible role of enterotoxin
 Clinical Features (contd.)
Dehydration is the main contributor to
mortality.

Secondary malabsorption of lactose and

fat, and chronic diarrhea are possible
 Diagnosis
Antigen detection in stool by ELISA, LA (for
Group A rotavirus)
EM- non-Group A viruses also
Culture- Group A rotaviruses can be cultured in
monkey kidney cells
Serology for epidemiologic studies
 Treatment and Prevention
Treatment-
Supportive- oral, IV rehydration

Prevention-
Handwashing and disinfection of
surfaces
 Vaccine
Live tetravalent rhesus-human reassortant vaccine
(Rotashield)
Licensed for use in August 1998
Removed from the market in October 1999 due to
risk of intussusception
Cases were seen 3-20 days after vaccination
Approx. 15 cases/1.5 million doses
GASTROENTERITIS DUE
TO ENTERIC ADENOVIRUS
GASTROENTERITIS DUE TO
ADENOVIRUS
Types 40, 41
Belong to serogroup F

Some cases due to types 31, 3, 7

 Diarrhea due to
Enteric Adenovirus
Age <4 years
Year round
Spread via fecal-oral route
 Clinical features of Enteric
Adenovirus gastroenteritis
Incubation period 3 -10 days
Diarrhea lasts for 10 -14 days
Can also cause intussusception, mesenteric
adenitis, appendicitis
Diagnosis- Enteric adenoviruses

Isolation requires special media-

Graham 293

ELISA for rapid detection is available

 HUMAN
CALICIVIRUSES
HUMAN CALICIVIRUSES
(HuCV)
Belong to Family Caliciviridae
Non-enveloped RNA viruses
with ss RNA
27-35 nm in size
Contain a single capsid protein
 HUMAN CALICIVIRUSES

Genomic analysis divides it into 4 groups

Human caliciviruses belong to 2 genera
CLASSIFICATION OF HuCV

NLV (Norovirus) SLV (Sapovirus)

Norwalk virus Sapporo virus
Hawaii virus Manchester virus
Snow Mountain virus Houston/86
Montgomery county virus London/92
Taunton (England)
 Morphology of HuCV-
typical

Typical morphology
32 cup-like depressions
EM appearance of Star of David
E.g.- Sapporo-like viruses
HUMAN CALICIVIRUSES - SLV
Morphology of HuCV-
atypical
Atypical morphology
Smooth surface
Small Round Structured viruses
E.g.- Norwalk-like viruses
SRSV- NORWALK VIRUS
 CLINICAL FEATURES
Adults and Children
Usual incubation Period is <24 hours
(ranges from 12hrs. to 4 days)
Short duration of illness <3 days
Nausea, vomiting, fever, headache
Abdominal cramping
Watery diarrhea
 Epidemiology-Noroviruses
Worldwide distribution
>23 million cases/year in the U.S.
Major cause of foodborne outbreaks of
GE
Most people have had infections by age
4 years (by seroprevalence studies)
 Spread of Norwalk virus
A. Person-to-person Fecal-oral spread
(stool/vomitus)
B. Fecal contamination of food or water
C. Spread through fomites?
 Epidemiology-Noroviruses
Asymptomatic infections- seroconversion but
asymptomatic shedding of virus
Low infective dose
Viral excretion during convalesence
(up to 2 weeks)
Ability to survive in water chlorination at
routine levels
Epidemiology of Outbreaks

Cruise ships, schools, nursing homes,

etc.
Can involve infants and school-age children
Source usually is contaminated food and
water (seafood-oyster and shellfish etc.)
 Diagnosis- Human Caliciviruses

Specimen- stool , vomitus, environmental

swabs, [not yet on foods]
Immune EM
RT-PCR in state public health labs.
Serology for epidemiologic purposes
 HUMAN
ASTROVIRUS
 ASTROVIRUS
Described in relation to an outbreak of
gastroenteritis in 1975
Detected by EM
Immunologically distinct from Human
Caliciviruses
Belong to family Astroviridae
8 human serotypes are known
 ASTROVIRUS- structure
Small ss RNA virus
Non-enveloped
27-32nm in size
Round with an unbroken, smooth surface
EM appearance of a 5 or 6 pointed star within
smooth edge
Contain 3 structural proteins
ASTROVIRUS- EM
STRUCTURE
 ASTROVIRUS - Epidemiology
Worldwide
Mainly in children <7 years of age.
Transmission person-to-person via
fecal-oral route
Outbreaks due to fecal contamination of
sea-food or water
ASTROVIRUS - Clinical Features

Infants and children are most often affected

Short incubation period 1-4 days
Nausea, vomiting, abdominal cramping and
watery diarrhea
Constitutional symptoms-fever, malaise,
headache
ASTROVIRUS - Diagnosis

EM (virus shed in stool in great

numbers)
EIA
RT-PCR