REOVIRUS -ROTAVIRUS

R.Varidianto Yudo T., dr.,MKes.

Lab. Mikrobiologi
Fakultas Kedokteran Universitas Hang Tuah
CHARACTERISTIC
Virion: Icosahedral, 6080 nm in diameter,
double capsid shell
Genome: Double-stranded RNA, linear,
segmented (1012 segments); total genome
size 1627 kbp
Proteins: Nine structural proteins; core
contains several enzymes. Main enzym is
RNA-dependent RNA polymerase
Envelope: None (transient pseudoenvelope is
present during rotavirus particle
morphogenesis)
 Gel diagram showing the 11 segments of the genome. The structural (VP)
and nonstructural (NSP) proteins encoded by these segments are indicated.
 Surface representation of the rotavirus structure from cryo-electron
microscopic analysis. The two outer layer proteins are VP4, which forms the
spikes, and VP7, which forms the capsid layer
Cut-away view showing the triple-layered organization of the virion, with the
intermediate VP6 layer and the innermost VP2 layer indicated. The enzymes
required for endogenous transcription (VP1) and capping (VP3) are attached
as heterodimeric complexes to the inner surface of the VP2 layer. Proposed
organization of the double-stranded RNA genome inside the VP2 layer along
with transcription enzyme complexes (VP1/3) depicted as balls.
 Exit of transcripts from the channels at the 5-fold vertices of actively
transcribing double-layered particles. Close-up view of one of the exit
channels.
REPLICATION
Reoviruses attach to the cell surface at the
site of the - adrenergic receptor.
Only the outer shell of the virus is removed,
and a core-associated RNA transcriptase is
activated.
This transcriptase transcribes mRNA
molecules from the minus strand of each
genome double-stranded RNA segment (10 or
11 segments) contained in the intact core.
Reovirus cores contain all enzymes necessary
for transcribing, capping, and extruding the
mRNAs from the core, leaving the double-
stranded RNA genome segments inside.
 Once extruded from the core, the mRNAs
are translated into primary gene products.
Some of the full-length transcripts are
encapsidated to form immature virus
particles.
A viral replicase is responsible for
synthesizing negative-sense strands to form
the double-stranded genome segments.
This replication to form progeny double-
stranded RNA occurs in partially completed
core structures.
 Rotavirus morphogenesis involves
budding of single-shelled particles into
the rough endoplasmic reticulum.
The "pseudoenvelopes" so acquired
are then removed and the outer capsids
are added
The virus is released from the
cytoplasm by lysis of the cell, not by
budding.
CLASSIFICATION
Rotaviruses have been classified into five
species (AE), plus two tentative species (F
and G), based on antigenic epitopes on the
internal structural protein VP6.
These can be detected by
immunofluorescence, ELISA, and
immune electron microscopy (IEM).
Group A rotaviruses are the most frequent
human pathogens.
PATHOGENESIS
Rotaviruses infect cells in the villi of the
small intestine (gastric and colonic mucosa
are spared).
They multiply in the cytoplasm of
enterocytes and damage their transport
mechanisms.
One of the rotavirus-encoded proteins,
NSP4, is a viral enterotoxin and induces
secretion by triggering a signal transduction
pathway.
 Damaged cells may slough into the
lumen of the intestine and release large
quantities of virus, which appear in the
stool (up to 1010 particles per gram of
feces).
Viral excretion usually lasts 212 days in
otherwise healthy patients but may be
prolonged in those with poor nutrition.
Diarrhea caused by rotaviruses may be due to
impaired sodium and glucose absorption
as damaged cells on villi are replaced by
nonabsorbing immature crypt cells.
It may take 38 weeks for normal function
to be restored.
EPIDEMIOLOGY & IMMUNITY
Rotaviruses are the single most important
worldwide cause of gastroenteritis in young
children. Developed countries have a high
morbidity rate but a low mortality rate.
Typically, up to 50% of cases of acute
gastroenteritis of hospitalized children
throughout the world are caused by
rotaviruses.
Rotavirus infections usually predominate
during the winter season. Transmission
appears to be by the fecal-oral route.
Nosocomial infections are frequent.
 Rotaviruses are ubiquitous. By age 3 years,
90% of children have serum antibodies to
one or more types. This high prevalence of
rotavirus antibodies is maintained in adults,
suggesting subclinical reinfections by the
virus.
Rotavirus reinfections are common; it has
been shown that young children can suffer up
to five reinfections by 2 years of age.
Asymptomatic infections are more common
with successive reinfections.
 Local immune factors, such as secretory IgA
or interferon, may be important in protection
against rotavirus infection.
Asymptomatic infections are common in
infants before age 6 months, the time during
which protective maternal antibody acquired
passively by newborns should be present.
Such neonatal infection does not prevent
reinfection, but it does protect against the
development of severe disease during
reinfection.
TREATMENT & CONTROL
Treatment of gastroenteritis is supportive, to correct
the loss of water and electrolytes that may lead to
dehydration, acidosis, shock, and death. Management
consists of replacement of fluids and restoration of
electrolyte balance either intravenously or orally, as
feasible. The infrequent mortality from infantile
diarrhea in developed countries is due to routine use
of effective replacement therapy.
In view of the fecal-oral route of transmission,
wastewater treatment and sanitation are significant
control measures.
An oral bovine-based rotavirus vaccine was licensed in
the United States. A safe and effective vaccine
remains the best hope for reducing the worldwide
burden of rotavirus disease.