REOVIRUSES

PREPARED BY : FRANCIS SM MAKANYA

FACILITATOR : DR. ABDALLAH BAJA

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 OUTLINE
• INTRODUCTION TO REOVIRUSES
• CLASSIFICATION AND ANTIGENIC PROPERTIES
• EPIDEMIOLOGY
• PATHOGENESIS
• ORBIVIRUSES
• COLTIVIRUS
• ORTHOREOVIRUSES
• REFERRENCES

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 INTRODUCTION
• The family Reoviridae is divided into nine genera, of which only four genera cause
human diseases.
• These genera are Orbivirus, Orthoreovirus, Rotavirus, and Coltivirus.
• Other genera infect only the plants, insects, and fish.
• The Reoviridae viruses are non-enveloped viruses with double-layered protein capsids.
The inner capsid layer shows well-defined subunits, whereas the outer layer of some
viruses (e.g., rotaviruses and orbiviruses) lacks these welldefined structures.
• The genome consists of a 10–12- segmented double-stranded RNA with a total genome
size of 16–27 kbp.
• The virus core contains many enzymes essential for transcription and capping of viral
RNA. These viruses are unusually resistant to heat, a wide pH (3.0–9.0), and to lipid
solvents but are sensitive to 95% ethanol, phenol, and chlorine.

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 CLASSIFICATION AND ANTIGENIC
PROPERTIES
• Reoviruses are ubiquitous, with a very wide range of mammalian,
avian, and reptilian hosts.
• Three distinct but related types of reovirus have been recovered from
many species and are demonstrable by neutralization and
hemagglutinationinhibition tests.
• Reoviruses contain a hemagglutinin for human group O or bovine
erythrocytes.

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 EPIDEMIOLOGY
• Reoviruses cause many inapparent infections because most people have
serum antibodies by early adulthood.
• Antibodies are also present in other species.
• All three types have been recovered from healthy children, from young
children during outbreaks of minor febrile illness, from children with enteritis
or mild respiratory disease, and from chimpanzees with epidemic rhinitis.
• Human volunteer studies have failed to demonstrate a clear cause-and-effect
relationship of reoviruses to human illness.
• In inoculated volunteers, reovirus is recovered far more readily from feces
than from the nose or throat.

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 PATHOGENESIS
• Reoviruses have become important model systems for the study of
the pathogenesis of viral infection at the molecular level.
• Defined recombinants from two reoviruses with differing pathogenic
phenotypes are used to infect mice.
• Segregation analysis is then used to associate particular features of
pathogenesis with specific viral genes and gene products.
• The pathogenic properties of reoviruses are primarily determined by
the protein species found on the outer capsid of the virion.

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 ORBIVIRUSES
• Orbiviruses are primarily animal pathogens that cause disease mainly in
animals. They are so named for their ring-shaped (Latin word orbi: ring)
structure.
• These viruses are differentiated from the orthoreoviruses by their
protein structure and their transmission by arthropod vectors.
• The genus Orbivirus consists of 19 species and at least 130 subspecies.
• The orbiviruses are nonenveloped viruses with two-layered capsids.
• The genome consists of 10 segments of double-stranded RNA.
• The virion measures 70–80 nm in diameter.

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Cont..
• Unlike other reoviruses, the orbiviruses are sensitive to low pH.
• The orbiviruses mainly cause disease in animals, such as sheep, cattle, goats,
and wild ungulates.
• They are associated with African horse sickness in horses, donkeys, and
dogs; blue tongue disease in sheep; and epizootic hemorrhagic fever in deer.
• Only few of orbiviruses are linked to disease in humans.
• Kemerovo virus has been implicated in neurological infections in Russia and
Central Europe.
• Lebombo virus, a virus isolated in Africa, has been implicated with clinical
disease in humans.

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Cont..
• Changuinola virus has been implicated in a single documented case
of an acute self-limited febrile illness in Panama. The disease is
transmitted by Phlebotomus flies.
• Orungovirus found in parts of Sub-Saharan Africa causes an acute
illness characterized by headache, fever, and myalgia. The virus is
transmitted primarily by Aedes mosquitoes.
• Oklahoma tick fever, reported in Oklahoma and Texas in the United
States, is transmitted by ticks. The condition manifests as fever,
nausea, and abdominal pain.

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Cont..
• The diagnostic facilities for orbivirus infections are available only in a
few reference laboratories.
• No specific antiviral agents are available.
• Use of insect repellants, protective clothing, and avoidance of tick bite
prevent transmission of orbivirus infections.

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 COLTIVIRUS
• Coltiviruses resemble the orbiviruses in their morphology and in
having two capsids.
• The genome consists of a 12-segmented double-stranded RNA.
• The coltiviruses associated with human disease include Colorado tick
fever, Salmon River virus, Banna virus, Beijing virus, Gansu virus, and
Eyach virus.

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Cont..
COLORADO TICK FEVER
• Colorado tick fever is an acute viral infection transmitted by the bite
of wood tick (Dermacentor andersoni) caused by Colorado tick fever
virus.
• Colorado fever was so named because the illness was believed to
occur predominantly in Colorado and was used to distinguish this
clinical illness from that of Rocky Mountain spotted fever caused by
Rickettsia species.
• The causative agent of this fever was recognized as a virus in 1946.

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Cont..
• Colorado tick fever virus is a double-stranded RNA virus surrounded
by two capsids.
• The virus contains 12 RNA segments.
• The virus infects and replicates in the bone marrow, lymph nodes,
spleen, and liver of rhesus monkey, but without producing any
histological abnormalities.
• The virus has been shown to replicate in erythroid precursor cells
without severely damaging them and is present in mature red blood
cells.

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Cont..
• Colorado tick fever occurs almost exclusively in the Western United
States and in Canada.
• The disease is transmitted by the bite of wood tick, D. andersoni.
• Larval and nymphal stages of D. andersoni ticks usually transmit the virus
among all rodents, but only adult ticks transmit the virus to humans.
• The ticks acquire the infection on feeding an infected viremic host.
• The infected ticks subsequently transmit the virus through their saliva
during act of feeding on a new susceptible host.
• Squirrels, rabbits, and deer are the natural animal hosts for the virus.

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Cont..
• The virus generally causes a nonspecific febrile illness.
• The incubation period is short and varies from 3 to 6 days.
• The clinical manifestations of the acute condition are characterized by
the sudden onset of fever, chills, headache with retro-orbital pain,
malaise, nausea, and occasionally vomiting.
• A rash is generally absent by which Colorado tick fever is
differentiated from the Rocky Mountain spotted fever.

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Cont..
• The fever is typically biphasic (i.e., with two episodes of fever), each
of which lasts 2–3 days, separated by a remission of approximately
equal duration.
• In most cases, the febrile period is followed by moderate to marked
weakness and malaise.
• Complications are rare, but may include hepatitis, pericarditis,
epididymo-orchitis, atypical pneumonitis, encephalitis, and aseptic
meningitis.

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Cont..
• Viruses are present in the erythrocytes during the first 2 weeks of
disease. This is followed by a period during which the viruses infect
and replicate within the erythropoietic cells.
• In the infected red blood cells, the viruses can live for the life of the
cells, which is nearly 120 days.
• A single attack of infection usually produces lifelong immunity.

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Cont..
• Laboratory diagnosis of Colorado tick fever is established by isolation
of the virus from the erythrocyte fraction of the whole blood.
• The virus has been shown to persist in erythrocytes for as long as 120
days.
• The virus has also been found in the cerebrospinal fluid of patients
with no apparent encephalitis or meningitis.
• The virus isolation, however, takes nearly 1–2 weeks.

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Cont..
• Neutralization test in suckling mice, tissue culture neutralization,
immunofluorescence, and enzyme immunoassay are various
serological tests used for demonstration of antibodies in the serum
for diagnosis of the condition.
• A fourfold increase in titer of the specimen during the acute phase
and convalescent phase is demonstrated in nearly all patients.

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Cont..
• No specific antiviral treatment is available for Colorado tick fever.
• The condition is usually self-limited and can be prevented by avoiding
contact with the wood tick.

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 ORTHOREOVIRUSES
• Orthoreoviruses are nonenveloped viruses, measuring 80 nm in diameter.
• It is composed of an inner protein shell, i.e., core and an outer protein
shell known as outer capsid.
• The inner core is composed of three major lipids,  γ1,  γ2, and δ2, and
many minor proteins.
• The core consists of a 10-segmented double-stranded RNA.
• The reoviruses have three serotypes, namely, type 1, 2, and 3, based on
neutralization and hemagglutination inhibition test.
• All these serotypes share a common complement fixation antigen.

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Cont..
• The reoviruses are very stable. They are stable to heat, to a wide
range of pH, and are also stable in aerosols.
• Reoviruses can be cultured in monkey kidney cells, HeLa cells, and
mouse L-cell fibroblast.

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Cont..
• Human volunteers’ studies have failed to establish a clear cause-and-
effect relationship between reoviruses and human illness.
• So far, reoviruses have been linked with upper respiratory infection,
fever, enteritis, and febrile exanthema in children.
• All three serotypes of the virus have been recovered from healthy
children and from children with minor febrile illness, diarrhea, or
enteritis.
• The exact method of transmission of reoviruses is not known.
• Since viruses are isolated most frequently from the feces, the infection
appears to be transmitted by the fecal–oral route.
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Cont..
• Recent studies have shown the potential of reovirus as an oncolytic
virus and have shown the susceptibility of transformed cell to reovirus
replication.
• It has been demonstrated that normal non-transformed cells were
resistant to the virus.
• Reovirus causes oncolysis (apoptotic cell death) in a wide variety of
cancer cells and tumors.

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Cont..
• Results of many studies have shown a possible role of reovirus in the
treatment of brain and leptomeningeal metastasis from breast cancer.
• The beneficial role of reovirus in reducing the sequential spinal and
leptomeningeal metastasis from medulloblastoma has also been
suggested.

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Cont..
• The laboratory diagnosis of the human orthoreovirus infection can be
made by:
1. The isolation of the virus and detection of the viral antigen and RNA
genome in various clinical specimens, such as feces, throat swabs, and
nasopharyngeal specimens.
2. The serological tests, such as hemagglutination inhibition,
complement fixation, or virus neutralization to demonstrate antibodies.
• These serological tests are used primarily for epidemiological studies.

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Cont..
• No specific treatment is available for orthoreovirus infection.
• No preventive measures have been suggested due to the lack of
definitive association of orthoreovirus with human disease.

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REFERRENCES

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