REOVIRUSES

The Reoviridiae is composed of a group of respiratory and enteric viruses that

were not associated with any known disease (respiratory, enteric, orphan).

The orthoreoviruses are also referred to They are nonenveloped viruses

as mammalian reoviruses or simply
reoviruses, and are the prototype of this
virus family.
Rotaviruses cause human infantile
gastroenteriris which is a very common
disease -50% of all cases of diarrhea in
children requiring hospitaliztion
because of dehydration.
with double-layered protein
capsids containing 10-12
segments of the dsRNA
genomes.
They are stable in detergents,
over wide pH and temperature
ranges and in airborne
aerosols.
 Rotaviruses and reovirues share many structural,
replicative and pathogenic features.

The name rotavirus is derived from the Latin word

rota, meaning “wheel”, which referes to the virion’s
appearance in negative-stained electron micrographs.
The outer capsid is composed of structural proteins
which surround a nucleocapsid core that includes
enzymes for RNA synthesis and 10 (reo) or 11 (rota)
ds RNA genomic segments.

For rotavirus, the outer capsid has two

layers, an intermediate layer consisting of
the major capsid protein (VP6) and an
outer layer that contains the viral
attachment protein (VP4) and
glycoprotein (VP7).

Each of the (-) sense RNA strands are used as
a template by virion core enzymes, which
synthesize individual (+) mRNAs.
The virion outer layer protects
the inner nucleocapsid and core
from the environment, especially
the acidic environment of the GI
tract. Proteolytic cleavage of the
outer capsid in GI tract activates
the virus for infection and
produces an
intermediate/infectious subviral
particle (ISVP).
Following the receptor-mediated
encytosis of the whole virion,
ISVP releases the core into the
cytoplasm and the enzymes in
the core initiate mRNA
production. The dsRNA always
remain in the core.
Virus-encoded enzymes within
the core add 5’-methyl
guanosine cap and a 3’
poladenylate tail. The mRNA
then leaves the core and is
translated. Virion proteins and
(+) mRNA segments associate
into core-like structures
(cytoplasmic inclusions).

(+) sense RNA segments are

copied to produce (-) RNAs in
the new cores, replicating the
ds genome. The new cores
either generate more (+) RNA
or are assembled into virions.

After adopting the outer capsid

both rota and reoviruses leave
the cell upon cell lysis.
ORTHOREOVIRUSES (MAMMALIAN REOVIRUSES)
The orthoreoviruses have been found worlwide such that most people are
probably infected during childhood--approximately 75% of adults have
antiviral antibody.

It is not known whether animals are a reservoir for human infections since
most animals are infected with reovirus that are serologically related to
human reovirus.
They are very stable and were detected in
sewage and river water.

The mammalian reoviruses occur in three

serotypes that differ in neutralization and
hemagglutination:
• Reovirus type I
• Reovirus type II
• Reovirus type III
All share common complement-fixing antigen.
They do not cause significant disease in humans. Most infections are
throught to be asymptomatic or are so mild they go undetected. Thus far,
viruses have been linked to common coldlike, mild, upper respiratory tract
illness, GI tract disease and biliary atresia.

The viruses are thought to bind to

M cells in small intestine, which
then transfer the virus to the
lymphoid tissue of Peyer
pathches lining the intestines.

The viruses then replicate and initiate a viremia. It causes few if any
symptoms before entering the circulation and producing infection at a
distant site.

Protective humoral and cellular immune responses to outer capsid

proteins are triggered.
The viruses can be detected through
• assay of the viral antigen or RNA in clinical material
• virus isolation
• serologic assays

Materials that can be used are from:

• Throat
• Nasopharyngeal, and
• Stool

Since orthoreovirus diseases are mild and self-limited,

treatment has not been necessary and prevention and
control measures have not been developed.
ROTAVIRUSES
Human and animal retroviruses are divided into seven
groups (A to G). Human disease is causes by group A and
occassionally group B and C rotaviruses:
Group A  widspread, winter infections
 infants younger than 24 months of age are at risk for infantile
gastroenteritis with potential dehydration
 older children and adults are at risk for mild diarrhea
 Undernourished people in underdeveloped countries suffer
from diarrhea, dehydration, death
Group B  especially adults, asympomatic in children,
several outbreaks of group B rotavirus have occured in
China because of contaminated water supplies
Group C  asymptomatic infections

Relatively stable to environmental abuse including

treatment with detergants, pH extremes of 3.5 to 10,
repeated freezing and thawing.
The virus survives well on fomites and on hands
because it can withstand drying. Although
domestic animals are known to harbor
serologically related rotaviruses, they are not
common source of human infection.
They are transmitted mosltly in Januray-February. Tranmission via fecal-oral
route.

Viral replication occurs after absorption of the ISVP to columnar epithelial

cells covering the vili of small intestine. Infections causes shortening and
blunting of the microvili and mononuclear cell infiltration.

Rotavirus infection prevents the absorption of water, causing a net secretion

of water and loss of ions, which together result in a watery diarrhea, severe
dehydration and even death if electrolyte replacement therapy is not
started.

Infection in infants and small children is generally symptomatic, whereas in

adults, it is usually asymptomatic.
Immunity to infection requires the presence of antibody, primarily IgA.
In step 1, neutralizing antibodies
directed against VP4 and/or VP7 can
prevent viral binding and penetration,
inducing viral exclusion.

During step 3, intracellular viral

replication can be inhibited by
secretory anti-VP6 immunoglobulin A
(IgA) during transcytosis across
enterocytes.
Actively or passively acquired antibody can lessen the severity of disease
but does not consistently prevent reinfection.

In the absence of antibody, the inoculation of even small amounts of virus

causes infection and diarrhea.

Duodenal fluid and serum virus-spesific IgM (1. week), IgA and IgG (1-4
weeks).
Rotavirus is a major cause of gastroenteritis. The major clinical
findings in hospitalized patients are
• vomitting
• diarrhea
• fever, and
• dehydration

Neither decal leukocytes nor blood occurs in stool.

Rotavirus gastroenteritis is a self-limited disease and recovery

is generally complete and without sequelae.

However infection may prove fatal in infants who live in

developing countries and who are malnourished and
dehydrated before the infection.
LABORATORY DIAGNOSIS
Most patients have large amounts of virus
in stool, and they can be detected by
• ELISA
• Latex agglutination
• Electron microscopy
• Immunoelectron microscopy
• RT-PCR

Cell culture requires pretreatment with trypsin to generate ISVP for

infection, however is not used for diagnostic purposes.

Serologic studies are primarily for research and epidemiologic purposes.

Because so many people have rotavrus-spesific antibody, a 4-fold rise is
necessary for diagnosis of recen tinfection or active disease.
TREATMENT, PREVENTION, and CONTROL
No specific therapy is available for a rotavirus infection. Since morbidity
and mortality associated result from dehydration and electrolyte
imbalance, supportive therapy to replace fluids should be initiated so
that blood volume and electrolyte and acid-base imbalances can be
corrected.

Hospitalized patients with disease must be isolated to limit spread of

the infection toother susceptible patients.

There are two rotaviruse vaccines in use:

(1) RotaTeq consist of five reassortant bovine retroviruses containing
two outer capsid peptides of five human retroviruses.
(2) The RotaRix is a single strain attenuated human rterovirus.

They are administered as young as possible, at 2, 4, and 6 months of

age.
 Rotarix By GlaxoSmithKline

Possible Side Effects

*Do not administer to infants who have immunodeficiencies*

 In rare cases infants taking Rotarix may be at risk for

intussusception*
*If the risk for U.S. infants is similar to that found in the Mexico study, it would
translate to 0 -4 cases of intussusception from vaccine per 100,000 U.S. infants who
receive the first dose of Rotarix.

İntussusception
an instance of the inversion of one portion of
the intestine within another.
Possible Side Effects
*Do not administer to infants who have immunodeficiencies*

Reports of “Kawasaki disease” - 5 cases during clinical trials & only 3

cases after the vaccine was approved out of a total of ~6 million doses that were
administered between 2006-2007
CDC and FDA have yet to link the vaccine to these cases and continue to support
routine immunization of all U.S. infants

Kawasaki disease is a rare

childhood illness that affects
the blood vessels.
COLTIVIRUSES and ORBIVIRUSES

The coltiviruses and orbiviruses infect verterbrates and invertebrates.

Coltiviruses  Colarado tick fever
Orbivirus cause disease in animals, including
blue tongue disease of sheep, African
horse sickness, and epizootic hemorrhagic
disease of deer.

Colarado tick fever which is an acute disease characterized by fever,

headache, and severe myalgia, is one of the most common tick-borne viral
diseases in the US.

Structures and physiologies are the same as other Reoviridea except for
(a) Orbivirus outer capsid has no capsomeric structure
(b) The orbivirus life cycle include verterbrates and invertebrates
The other distinguishing feature of Colarado rick
fever virus is that they can infect erythroid
precursor cells without severely damaging
them.

The virus remains within the cells, even after

they mature into RBCs; this factor protectes the
virus from clearance.

Serious hemorrhagic disease can result from

the infection of vacular endothelial cand
vascular smooth muscle cells and pericytes,
thereby weakening capillary structure.

The weakness leads to hemorrhage, and potentially hypertension and

shock. Neuronal infection can lead ot meningitis and encaphalitis.
Ticks acquire the virus by feeding on a
viremic host and subsequently transmit
the virus by feeding on a viremic host
and subsequently transmit the virus in
saliva when feeding on a new host.

Natural hosts include many mammals

including
• squirrels
• chipmunks
• rabbits
• deer

Human disease is observed during the spring, summer and autumn,

seasons when humans are more likely to invade the habitat of the tick.
 After 3-6 day incubation period, symptomatic infections start with the
sudden onset of fever, chills, headache, photophobia, myalgia, arthralgia,
and lethargy.
Characteristic of the infection include biphasic fever,
conjunctivitis and possibly lymphoadenopathy,
hepatosplenomegaly and a maculopapular rash.

Leukopenia involving both neutrophils and lymphocytes is an important

hallmark of the disease.

Children occasionally have a more severe hemorrhagic disease.

 LABORATORY DIAGNOSIS
A diagnosis of Colarado tick fever can be establised through
• the direct detection of viral antigens
• virus islation
• serologic tests

The best, most rapid method is detection

of viral antigen on the surfaces of
erythrocytes in a blood smear through the
use of immunflourescence.

For subclinical infections, the titers of antibody in acute and covalescent

speciemtns must be compared (antibody may persist for lifetime). Spesific
IgM can be detected approximately 45 days after the onser of illnesss.

Besides of immunoflourescence complement fixation, neutralization, and

ELISA can also be ued to detect antibodies.
TREATMENT, PREVENTION, and CONTROL

There is not a virus-spesific treatment. Since the disease is self-limited,

supportive care is sufficient.

In order to minimize the spread, recovered patients should not be

allowed to donate blood as the viremie is long lasting. Other measures
for prevention include
• avoiding tick-infested areas
• using protective clothing and tick repellents
• removing ticks before they bite.

A Colorado tick fever vaccine has been developed and evaluated, but
because of the milness of the disease, its distribution to the general
public is not warranted.