Download 40. RNA Non-enveloped Viruses

PICORNAVIRUSES: INTRODUCTION
Picornaviruses are small (20–30 nm) nonenveloped viruses composed of
an icosahedral nucleocapsid and a single-stranded RNA genome. The
genome RNA has positive polarity; i.e., on entering the cell, it functions as the
viral mRNA. The genome RNA is unusual because it has a protein on the 5' end
that serves as a primer for transcription by RNA polymerase. Picornaviruses
replicate in the cytoplasm of cells. They are not inactivated by lipid solvents, such
as ether, because they do not have an envelope.
The picornavirus family includes two groups of medical importance:
the enteroviruses and the rhinoviruses. Among the major enteroviruses are
poliovirus, coxsackieviruses, echoviruses, and hepatitis A virus (which is
described in Chapter 41). Enteroviruses infect primarily the enteric tract, whereas
rhinoviruses are found in the nose and throat (rhino = nose).
Important features of viruses that commonly infect the intestinal tract are
summarized in Table 40–1. Enteroviruses replicate optimally at 37°C, whereas
rhinoviruses grow better at 33°C, in accordance with the lower temperature of
the nose. Enteroviruses are stable under acid conditions (pH 3–5), which enables
them to survive exposure to gastric acid, whereas rhinoviruses are acid-labile.
This explains why rhinovirus infections are restricted to the nose and throat.
Table 40–1. Features of Viruses Commonly Infecting the
Intestinal Tract.
Virus
Nuclei
c Acid
Disease
Number Lifelong Vaccine Antivira
of
Immunit Availabl
l
Serotype
y to
e
Therap
s
Disease
y
Poliovirus
RNA
Poliomyeliti 3
s
Yes (type- +
specific)
–
Echoviruses
RNA
Meningitis,
etc
Many
No
–
–
Coxsackieviruse RNA
s
Meningitis, Many
carditis, etc
No
–
–
Hepatitis A
virus
(enterovirus
72)
Hepatitis
Yes
+
–
RNA
1
Rotavirus
RNA
Diarrhea
Several1
No
–2
–
Norwalk virus
(Norovirus)
RNA
Diarrhea
Unknown
No
–
–
Adenovirus
DNA
Diarrhea
41; of
which 2
cause
diarrhea
Unknown
–
–
Exact number uncertain.
1
Rotavirus vaccine was released but was withdrawn because of side effects (see
text).
2
ENTEROVIRUSES
Poliovirus
Disease
This virus causes poliomyelitis.
Important Properties
The host range is limited to primates, i.e., humans and
nonhuman primates such as apes and monkeys. This limitation is due to the
binding of the viral capsid protein to a receptor found only on primate cell
membranes. However, note that purified viral RNA (without the capsid protein)
can enter and replicate in many nonprimate cells—the RNA can bypass the cell
membrane receptor; i.e., it is "infectious RNA."
There are three serologic (antigenic) types based on different antigenic
determinants on the outer capsid proteins. Because there is little cross-reaction,
protection from disease requires the presence of antibody against each of the
three types.
Summary of Replicative Cycle
The virion interacts with specific cell receptors on the cell membrane and then
enters the cell. The capsid proteins are then removed. After uncoating, the
genome RNA functions as mRNA and is translated into one very large
polypeptide called noncapsid viral protein 00. This polypeptide is cleaved by a
virus-encoded protease in multiple steps to form both the capsid proteins of the
progeny virions and several noncapsid proteins, including the RNA polymerase
that synthesizes the progeny RNA genomes. Replication of the genome occurs by
synthesis of a complementary negative strand, which then serves as the template
for the positive strands. Some of these positive strands function as mRNA to
make more viral proteins, and the remainder become progeny virion genome
RNA. Assembly of the progeny virions occurs by coating of the genome RNA with
capsid proteins. Virions accumulate in the cell cytoplasm and are released upon
death of the cell. They do not bud from the cell membrane.
Transmission & Epidemiology
Poliovirus is transmitted by the fecal–oral route. It replicates in the oropharynx
and intestinal tract. Humans are the only natural hosts.
As a result of the success of the vaccine, poliomyelitis caused by naturally
occurring "wild-type" virus has been eradicated from the United States and,
indeed, from the entire Western hemisphere. The rare cases in the United
States occur mainly in (1) people exposed to virulent revertants of the attenuated
virus in the live vaccine and (2) unimmunized people exposed to "wild-type"
poliovirus while traveling abroad. Before the vaccine was available, epidemics
occurred in the summer and fall.
The World Health Organization set the eradication of paralytic polio by 2005 as a
goal. Unfortunately, as of 2007, paralytic polio still exists in 16 countries, but its
incidence is greatly reduced. In 1988, there were 388,000 cases of paralytic polio
worldwide, whereas in 2005 there were fewer than 2000. Thus far, smallpox is
the only infectious disease that has been eradicated, a consequence of the
worldwide use of the smallpox vaccine.
Pathogenesis & Immunity
After replicating in the oropharynx and small intestine, especially in lymphoid
tissue, the virus spreads through the bloodstream to the central nervous system.
It can also spread retrograde along nerve axons.
In the central nervous system, poliovirus preferentially replicates in the motor
neurons located in the anterior horn of the spinal cord. Death of these cells
results in paralysis of the muscles innervated by those neurons. Paralysis is not
due to virus infection of muscle cells. The virus also affects the brain stem,
leading to "bulbar" poliomyelitis (with respiratory paralysis), but rarely damages
the cerebral cortex.
In infected individuals, the immune response consists of both intestinal IgA and
humoral IgG to the specific serotype. Infection provides lifelong type-specific
immunity.
Clinical Findings
The range of responses to poliovirus infection includes (1) inapparent,
asymptomatic infection; (2) abortive poliomyelitis; (3) nonparalytic poliomyelitis;
and (4) paralytic poliomyelitis. Asymptomatic infection is quite common. Roughly
1% of infections are clinically apparent. The incubation period is usually 10–14
days.
The most common clinical form is abortive poliomyelitis, which is a mild, febrile
illness characterized by headache, sore throat, nausea, and vomiting. Most
patients recover spontaneously. Nonparalytic poliomyelitis manifests as aseptic
meningitis with fever, headache, and a stiff neck. This also usually resolves
spontaneously. In paralytic poliomyelitis, flaccid paralysis is the predominant
finding, but brain stem involvement can lead to life-threatening respiratory
paralysis. Painful muscle spasms also occur. The motor nerve damage is
permanent, but some recovery of muscle function occurs as other nerve cells
take over. In paralytic polio, both the meninges and the brain parenchyma
(meningoencephalitis) are often involved. If the spinal cord is also involved, the
term meningomyeloencephalitis is often used.
A post-polio syndrome that occurs many years after the acute illness has been
described. Marked deterioration of the residual function of the affected muscles
occurs many years after the acute phase. The cause of this deterioration is
unknown.
No permanent carrier state occurs following infection by poliovirus, but virus
excretion in the feces can occur for several months.
Laboratory Diagnosis
The diagnosis is made either by isolation of the virus or by a rise in antibody
titer. Virus can be recovered from the throat, stool, or spinal fluid by inoculation
of cell cultures. The virus causes a cytopathic effect (CPE) and can be identified
by neutralization of the CPE with specific antisera.
Treatment
There is no antiviral therapy. Treatment is limited to symptomatic relief and
respiratory support, if needed. Physiotherapy for the affected muscles is
important.
Prevention
Poliomyelitis can be prevented by both the killed vaccine (Salk vaccine,
inactivated vaccine, IPV) and the live, attenuated vaccine (Sabin vaccine, oral
vaccine, OPV) (Table 40–2). Both vaccines induce humoral antibodies, which
neutralize virus entering the blood and hence prevent central nervous system
infection and disease. Both the killed and the live vaccines contain all three
serotypes. At present, the inactivated vaccine is preferred for reasons that are
described below.
Table 40–2. Important Features of Poliovirus Vaccines.
Attribute
Killed
(Salk)
Live
(Sabin)
Prevents disease
Yes
Yes
Interrupts transmission
No
Yes
Induces humoral IgG
Yes
Yes
Induces intestinal IgA
No
Yes
Affords secondary protection by spread to others
No
Yes
Interferes with replication of virulent virus in gut
No
Yes
Reverts to virulence
No
Yes (rarely)
Coinfection with other enteroviruses may impair
immunization
No
Yes
Can cause disease in the immunocompromised
No
Yes
Route of administration
Injection
Oral
Requires refrigeration
No
Yes
Duration of immunity
Shorter
Longer
The current version of the inactivated vaccine is called enhanced polio
vaccine, or eIPV. It has a higher seroconversion rate and induces a higher titer
of antibody than the previous IPV. eIPV also induces some mucosal immunity
IgA, making it capable of interrupting transmission, but the amount of secretory
IgA induced by eIPV is significantly less than the amount induced by OPV. OPV is
therefore preferred for eradication efforts. The only version of polio vaccine
currently produced in the United States is eIPV. In certain countries where polio
remains endemic (e.g., India), a monovalent oral polio vaccine is used because
the rate of seroconversion is higher with the monovalent vaccine than with the
trivalent one.
In the past, the live vaccine was preferred in the United States for two main
reasons. (1) It interrupts fecal–oral transmission by inducing secretory IgA in the
gastrointestinal tract. (2) It is given orally and so is more readily accepted than
the killed vaccine, which must be injected.
The live vaccine has four disadvantages: (1) Rarely, reversion of the attenuated
virus to virulence will occur, and disease may ensue (especially for the type 3
virus); (2) it can cause disease in immunodeficient persons and therefore should
not be given to them; (3) infection of the gastrointestinal tract by other
enteroviruses can limit replication of the vaccine virus and reduce protection; and
(4) it must be kept refrigerated to prevent heat inactivation of the live virus.
Outbreaks of paralytic polio caused by vaccine-derived poliovirus (VDPV) continue
to occur, especially in areas where there are large numbers of unimmunized
people. These VDPV strains have lost their attenuation by acquiring genes from
wild type enteroviruses by recombination. Outbreaks of VDPV-associated
paralytic polio have been contained by campaigns to immunize people in the
affected area with the oral (Sabin) vaccine that interrupts fecal–oral
transmission.
The duration of immunity is thought to be longer with the live than with the killed
vaccine, but a booster dose is recommended with both.
The currently approved vaccine schedule consists of four doses of inactivated
vaccine administered at 2 months, 4 months, 6–18 months, and upon entry to
school at 4–6 years. One booster (lifetime) is recommended for adults who travel
to endemic areas. The use of the inactivated vaccine should prevent some of the
approximately 10 cases per year of vaccine-associated paralytic polio that arise
from reversion of the attenuated virus in the vaccine. In the past, some lots of
poliovirus vaccines were contaminated with a papovavirus, SV40 virus, which
causes sarcomas in rodents. SV40 virus was a "passenger" virus in the monkey
kidney cells used to grow the poliovirus for the vaccine. Fortunately, no increase
in cancer occurred in persons inoculated with the SV40 virus–containing polio
vaccine. However, there is some evidence that SV40 DNA can be found in certain
human cancers such as non-Hodgkin's lymphoma; the role of SV40 as a cause of
cancer in persons immunized with early versions of the polio vaccine is
unresolved. At present, cell cultures used for vaccine purposes are carefully
screened to exclude the presence of adventitious viruses.
Passive immunization with immune serum globulin is available for protection of
unimmunized individuals known to have been exposed. Passive immunization of
newborns as a result of passage of maternal IgG antibodies across the placenta
also occurs.
Quarantine of patients with disease is not effective, because fecal excretion of the
virus occurs in infected individuals prior to the onset of symptoms and in those
who remain asymptomatic.
Coxsackieviruses
Coxsackieviruses are named for the town of Coxsackie, NY, where they were first
isolated.
Diseases
Coxsackieviruses cause a variety of diseases. Group A viruses cause, for
example, herpangina, acute hemorrhagic conjunctivitis, and hand-foot-andmouth disease, whereas group B viruses cause pleurodynia, myocarditis, and
pericarditis. Both types cause nonspecific upper respiratory tract disease
(common cold), febrile rashes, and aseptic meningitis.
Important Properties
Group classification is based on pathogenicity in mice. Group A viruses cause
widespread myositis and flaccid paralysis, which is rapidly fatal, whereas group B
viruses cause generalized, less severe lesions of the heart, pancreas, and central
nervous system and focal myositis. At least 24 serotypes of coxsackievirus A and
6 serotypes of coxsackievirus B are recognized.
The size and structure of the virion and the nature of the genome RNA are similar
to those of poliovirus. Unlike poliovirus, they can infect mammals other than
primates.
Summary of Replicative Cycle
Replication is similar to that of poliovirus.
Transmission & Epidemiology
Coxsackieviruses are transmitted primarily by the fecal–oral route, but
respiratory aerosols also play a role. They replicate in the oropharynx and the
intestinal tract. Humans are the only natural hosts. Coxsackievirus infections
occur worldwide, primarily in the summer and fall.
Pathogenesis & Immunity
Group A viruses have a predilection for skin and mucous membranes, whereas
group B viruses cause disease in various organs such as the heart, pleura,
pancreas, and liver. Both group A and B viruses can affect the meninges and the
motor neurons (anterior horn cells) to cause paralysis. From their original site of
replication in the oropharynx and gastrointestinal tract, they disseminate via the
bloodstream.
Immunity following infection is provided by type-specific IgG antibody.
Clinical Findings
GROUP A–SPECIFIC DISEASES
Herpangina is characterized by fever, sore throat, and tender vesicles in the
oropharynx. Hand-foot-and-mouth disease is characterized by a vesicular rash on
the hands and feet and ulcerations in the mouth, mainly in children.
GROUP B–SPECIFIC DISEASES
Pleurodynia (Bornholm disease, epidemic myalgia, "devil's grip") is
characterized by fever and severe pleuritic-type chest pain. Myocarditis and
pericarditis are characterized by fever, chest pain, and signs of congestive failure.
Dilated cardiomyopathy with global hypokinesia of the myocardium is a feared
sequel that often requires cardiac transplantation to sustain life. Diabetes in
mice can be caused by pancreatic damage as a result of infection with
coxsackievirus B4. This virus is suspected to have a similar role in juvenile
diabetes in humans.
DISEASES CAUSED BY BOTH GROUPS
Both groups of viruses can cause aseptic meningitis, mild paresis, and acute
flaccid paralysis similar to poliomyelitis. Upper respiratory infections and minor
febrile illnesses with or without rash can occur also.
Laboratory Diagnosis
The diagnosis is made either by isolating the virus in cell culture or suckling mice
or by observing a rise in titer of neutralizing antibodies. A rapid (2.5 hour) PCRbased test for enteroviral RNA in the spinal fluid is useful for making a prompt
diagnosis of viral meningitis because culture techniques typically take days to
obtain a result.
Treatment & Prevention
There is neither antiviral drug therapy nor a vaccine available against these
viruses. No passive immunization is recommended.
Echoviruses
The prefix ECHO is an acronym for enteric cytopathic human orphan. Although
called "orphans" because they were not initially associated with any disease, they
are now known to cause a variety of diseases such as aseptic meningitis, upper
respiratory tract infection, febrile illness with and without rash, infantile diarrhea,
and hemorrhagic conjunctivitis.
The structure of echoviruses is similar to that of other enteroviruses. More than
30 serotypes have been isolated. In contrast to coxsackieviruses, they are not
pathogenic for mice. Unlike polioviruses, they do not cause disease in monkeys.
They are transmitted by the fecal–oral route and occur worldwide. Pathogenesis
is similar to that of the other enteroviruses.
Along with coxsackieviruses, echoviruses are one of the leading causes of
aseptic (viral) meningitis. The diagnosis is made by isolation of the virus in
cell culture. Serologic tests are of little value, because there are a large number
of serotypes and no common antigen. There is no antiviral therapy or vaccine
available.
Other Enteroviruses
In view of the difficulty in classifying many enteroviruses, all new isolates have
been given a simple numerical designation since 1969.
Enterovirus 70 is the main cause of acute hemorrhagic conjunctivitis,
characterized by petechial hemorrhages on the bulbar conjunctivas. Complete
recovery usually occurs, and there is no therapy.
Enterovirus 71 is one of the leading causes of viral central nervous system
disease, including meningitis, encephalitis, and paralysis. It also causes diarrhea,
pulmonary hemorrhages, hand-foot-and-mouth disease, and herpangina.
Enterovirus 72 is hepatitis A virus, which is described in Chapter 41.
RHINOVIRUSES
Disease
These viruses are the main cause of the common cold.
Important Properties
There are more than 100 serologic types. They replicate better at
33°C than at 37°C, which explains why they affect primarily the nose and
conjunctiva rather than the lower respiratory tract. Because they are acidlabile, they are killed by gastric acid when swallowed. This explains why they do
not infect the gastrointestinal tract, unlike the enteroviruses. The host range is
limited to humans and chimpanzees.
Summary of Replicative Cycle
Replication is similar to that of poliovirus. The cell surface receptor for
rhinoviruses is ICAM-1, an adhesion protein located on the surface of many types
of cells.
Transmission & Epidemiology
There are two modes of transmission for these viruses. In the past, it was
accepted that they were transmitted directly from person to person via aerosols
of respiratory droplets. However, now it appears that an indirect mode, in which
respiratory droplets are deposited on the hands or on a surface such as a table
and then transported by fingers to the nose or eyes, is also important.
The common cold is reputed to be the most common human infection, although
data are difficult to obtain because it is not a well-defined or notifiable disease.
Millions of days of work and school are lost each year as a result of "colds."
Rhinoviruses occur worldwide, causing disease particularly in the fall and winter.
The reason for this seasonal variation is unclear. Low temperatures per se do not
predispose to the common cold, but the crowding that occurs at schools, for
example, may enhance transmission during fall and winter. The frequency of
colds is high in childhood and tapers off during adulthood, presumably because of
the acquisition of immunity.
A few serotypes of rhinoviruses are prevalent during one season, only to be
replaced by other serotypes during the following season. It appears that the
population builds up immunity to the prevalent serotypes but remains susceptible
to the others.
Pathogenesis & Immunity
The portal of entry is the upper respiratory tract, and the infection is limited to
that region. Rhinoviruses rarely cause lower respiratory tract disease, probably
because they grow poorly at 37°C.
Immunity is serotype-specific and is a function of nasal secretory IgA rather than
humoral antibody.
Clinical Findings
After an incubation period of 2–4 days, sneezing, nasal discharge, sore throat,
cough, and headache are common. A chilly sensation may occur, but there are
few other systemic symptoms. The illness lasts about 1 week. Note that other
viruses such as coronaviruses, adenoviruses, influenza C virus, and
coxsackieviruses also cause the common cold syndrome.
Laboratory Diagnosis
Diagnosis can be made by isolation of the virus from nasal secretions in cell
culture, but this is rarely attempted. Serologic tests are not done.
Treatment & Prevention
No specific antiviral therapy is available. Vaccines appear impractical because of
the large number of serotypes. Paper tissues impregnated with a combination of
citric acid (which inactivates rhinoviruses) and sodium lauryl sulfate (a detergent
that inactivates enveloped viruses such as influenza virus and respiratory
syncytial virus) limit transmission when used to remove viruses from fingers
contaminated with respiratory secretions. High doses of vitamin C have little
ability to prevent rhinovirus-induced colds. Lozenges containing zinc gluconate
are available for the treatment of the common cold, but their efficacy remains
unproved.
CALICIVIRUSES: INTRODUCTION
Caliciviruses are small, nonenveloped viruses with single-stranded RNA of
positive polarity. Although they share those features with picornaviruses,
caliciviruses are distinguished from picornaviruses by having a larger genome and
having distinctive spikes on the surface. There are two human pathogens in the
Calicivirus family: Norwalk virus and hepatitis E virus. Hepatitis E virus is
described in Chapter 41.
NORWALK VIRUS (NOROVIRUS)
Disease
Norwalk virus (also known as Norovirus) is one of the most common causes of
viral gastroenteritis in adults worldwide. It is named for an outbreak of
gastroenteritis in a school in Norwalk, Ohio, in 1969.
Important Properties
Norwalk virus has a nonsegmented, single-stranded, positive-polarity RNA
genome. It is a nonenveloped virus with an icosahedral nucleocapsid. There is no
virion polymerase. In the electron microscope, 10 prominent spikes and 32 cupshaped depressions can be seen. The number of serotypes is uncertain.
Summary of Replicative Cycle
Norwalk virus has not been grown efficiently in cell culture, so its replicative cycle
has been difficult to study. It is presumed to replicate in a manner similar to that
of picornaviruses.
Transmission & Epidemiology
Norwalk virus is transmitted by the fecal–oral route, often involving the ingestion
of contaminated seafood or water. Outbreaks typically occur in group settings
such as cruise ships (especially in the Caribbean region), schools, camps,
hospitals, and nursing homes. Person-to-person transmission also occurs,
especially in group settings. There are many animal caliciviruses, but there is no
evidence that they cause human infection.
Infection is enhanced by several features of the virus: low infectious dose,
excretion of virus in the stool for several weeks after recovery, and resistance to
inactivation by chlorination and to drying in the environment. It is thought to
remain infectious for several days on environmental surfaces such as door
handles.
Pathogenesis & Immunity
Norwalk virus infection is typically limited to the mucosal cells of the intestinal
tract. Watery diarrhea without red cells or white cells occurs. Many asymptomatic
infections occur, as determined by the detection of antibodies. Immunity
following infection appears to be brief and reinfection can occur.
Clinical Findings
Disease is characterized by sudden onset of vomiting and diarrhea accompanied
by low-grade fever and abdominal cramping. Neither the emesis nor the stool
contain blood. The illness typically lasts several days and there are no long-term
sequelae, except in certain immunocompromised patients in whom a prolonged
infection can occur. In some outbreaks, certain patients manifest signs of central
nervous system involvement such as headache, meningismus, photophobia, and
obtundation.
Laboratory Diagnosis
The diagnosis is primarily a clinical one. A polymerase chain reaction (PCR)-based
test on the stool is performed primarily when there are public health implications.
Treatment & Prevention
There is no antiviral therapy or vaccine available. Dehydration and electrolyte
imbalance caused by the vomiting and diarrhea may require intravenous fluids.
Personal hygiene, such as hand washing, and public health measures, such as
proper sewage disposal, are likely to be helpful.
REOVIRUSES: INTRODUCTION
REO is an acronym for respiratory enteric orphan; when the virus was discovered,
it was isolated from the respiratory and enteric tracts and was not associated
with any disease. Rotaviruses are the most important human pathogens in the
reovirus family.
ROTAVIRUS
Disease
Rotavirus is the most common cause of viral gastroenteritis in young children.
Important Properties
Reoviruses, including rotavirus, are composed of a segmented,1 doublestranded RNA genome surrounded by a double-layered icosahedral capsid
without an envelope.
The virion contains an RNA-dependent RNA polymerase. A virion polymerase
is required because human cells do not have an RNA polymerase that can
synthesize mRNA from a double-stranded RNA template.
Many domestic animals are infected with their own strains of rotaviruses, but
these are not a source of human disease. There are at least six serotypes of
human rotavirus. The outer surface protein (also known as the viral
hemagglutinin) is the type-specific antigen and elicits protective antibody.
Summary of Replicative Cycle
Reoviruses attach to the cell surface at the site of the -adrenergic receptor.
After entry of the virion into the cell, the RNA-dependent RNA polymerase
synthesizes mRNA from each of the 10 or 11 segments within the cytoplasm. The
10 or 11 mRNAs are translated into the corresponding number of structural and
nonstructural proteins. One of these, an RNA polymerase, synthesizes minus
strands that will become part of the genome of the progeny virus. Capsid proteins
form an incomplete capsid around the minus strands, and then the plus strands
of the progeny genome segments are synthesized. The virus is released from the
cytoplasm by lysis of the cell, not by budding.
Transmission & Epidemiology
Rotavirus is transmitted by the fecal–oral route. Infection occurs worldwide, and
by age 6 years most children have antibodies to at least one serotype.
Pathogenesis & Immunity
Rotavirus replicates in the mucosal cells of the small intestine, resulting in the
excess secretion of fluids and electrolytes into the bowel lumen. The consequent
loss of salt, glucose, and water leads to diarrhea. No inflammation occurs, and
the diarrhea is nonbloody. It is thought that this watery diarrhea is caused
primarily by stimulation of the enteric nervous system.
The virulence of certain reoviruses in mice has been localized to the proteins
encoded by several specific genome segments. For example, one gene governs
tissue tropism, whereas another controls the inhibition of cell RNA and protein
synthesis.
Immunity to rotavirus infection is unclear. It is likely that intestinal IgA directed
against specific serotypes protects against reinfection and that colostrum IgA
protects newborns up to the age of 6 months.
Clinical Findings
Rotavirus infection is characterized by nausea, vomiting, and watery, nonbloody
diarrhea. Gastroenteritis is most serious in young children, in whom
dehydration and electrolyte imbalance are a major concern. Adults usually have
minor symptoms.
Laboratory Diagnosis
Although the diagnosis of most cases of viral gastroenteritis does not involve the
laboratory, a diagnosis can be made by detection of rotavirus in the stool by
using radioimmunoassay or ELISA. This approach is feasible because there are
large numbers of virus particles in the stool. The original demonstration of
rotavirus in the stool was done by immunoelectron microscopy, in which antibody
aggregated the virions, allowing them to be visualized in the electron microscope.
This technique is not feasible for routine clinical use. In addition to antigen
detection, the diagnosis can be made by observation of a 4-fold or greater rise in
antibody titer. Although the virus can be cultured, this procedure is not routinely
done.
Treatment & Prevention
In 2006, the FDA approved a live rotavirus vaccine (RotaTeq) that contains five
human rotavirus strains. The immunogen in the vaccine virus is the outer surface
protein. The vaccine is given orally and the vaccine virus replicates in the small
intestine.
The five rotaviruses in the vaccine are reassortants in which the gene for the
human outer surface protein is inserted into a bovine strain of rotavirus. (Recall
that rotavirus has a segmented genome.) The bovine strain is nonpathogenic for
humans, but the human outer surface protein in the vaccine virus elicits
protective (IgA) immunity in the GI tract.
A previously approved vaccine (Rotashield) was withdrawn when a high rate of
intussusception occurred in vaccine recipients. Hygienic measures such as proper
sewage disposal and hand washing are helpful. There is no antiviral therapy.
Rotaviruses have 11 segments; other reoviruses have 10.
1