RNA VIRUS: PICORNAVIRUS and REOVIRUS

Ley Andrea Arranz & Joeperl Verdadero

PICORNAVIRUS PICORNAVIRUS REPLICATION CYCLE

• ssRNA (+) sense, naked, icosahedral symmetry • Occurs in the cytoplasm of the host's cell
• Very large virus family in terms of number of members
• Smallest virion (size)
• Two major groups of Human pathogens

GROUPS
1. Enteroviruses
2. Rhinoviruses

• Both are:
a) Inactivated when heated at 55° C
b) Can be reverted back
- stabilize by addition of Magnesium Chloride

Enterovirus
• Is stable at acidic ph (3.0 - 5.0 pH), at 1-3 hrs
• Transient in habitant of:
1. GIT 1. Virus attaches itself in its specific receptor located on the
2. Throat plasma membrane of the host's cell
Enterovirus
Rhinovirus •Specific receptors:members of Immunoglobulin superfamily
• Acid labile -- involves different antibodies, surface adhesion molecules)
• Inhabits the:
Echovirus
1. Nose • Main receptor site: Integrin Adhesion superfamily
2. Throat
2. Virus releases its RNA and VPg (Viral Protein genes)
STRUCTURE 3. VPg undergoes translation process to become specific
• observed in X- ray proteins.
4. Viral proteins are found on the capsid
- important as its antigenic site, involved in neutralization of
viral sample

ENTEROVIRUS GROUP
Polioviruses
• Causative agent of poliomyelitis
• Most infections are subclinical (no s/sx)
• Acute infectious disease that in its serious form affects the
central nervous system (CNS)
• Critical / serious infection: Destrution of motor neurons in the
spinal cord results in flaccid paralysis

• Each structure is made of Capsid shell PATHOGENESIS & PATHOLOGY

- provided with 60 subunits • Portal of entry: mouth
- each subunit contains 4 viral proteins • Primary multiplication: oropharynx or intestine*
• How does the virus reaches CNS?
Major protein grp: VP1 to VP3 - Mainly believed that initial multiplication happens in the
- main antigenic site involved in Neutralization process of vital tonsils, spreads to the lymph nodes
infection -- neck: lymphadenopathy
1. VP1 3. VP3 - further spreads to the peyer's patches, to the small
2. VP2 4. VP4 intestine, will enter the blood, and can now affect the CNS
Canyon
• prominent cleft in the virus' structure - In the CNS, virus will spread along the axons of the peripheral
• Serves as main receptor for attachment of virion to the nerve.
host cell - The peripheral nerve is composed of the spinal cord & brain.
• One of the most crucial part for adherence if virus - The virus will invade the nerve cell
-- Intracellular multiplication of the virus occurs, result to
• Picornavidae family contains 12 genera 1. Nerve damage, may lead to
1. Enterovirus 4. Kobuvirus 2. Paralysis (flaccid)
• Poliovirus • Aichivirus
• Coxsackie virus 5. Parechovirus • Virus is regularly present in the throat & in stools before the
2. Rhinovirus genus 6. Aphthovirus onset of illness
3. Hepatovirus 7. Cardiovirus
• Hepatitis A virus HERKCAP Poliovirus - it' continuously excreted/shredded in the stool for
several weeks even after Antibody production
• Causative agents of important human infections from
Enterovirus to Parechovirus  #1. Control mechanism - proper disposal of stool as it may
be a source of infection
RNA VIRUS: PICORNAVIRUS and REOVIRUS
Ley Andrea Arranz & Joeperl Verdadero

 Antibody production occurs before paralysis (CNS 2. SALK vaccine

invasion) • Injected
• Virus may be found in the blood of patient's with non- • Killed vaccine
paralystic poliomyelitis as samples • Given to immunocompromised patients
• Not all will cause paralysis, only if virus reaches CNS
Coxsackieviruses
CLINICAL FINDING • Large subgroup of the enteroviruses which is divided into two
groups
1. Mild Disease
• Total of 27 members
• Most common form
Group A
• Flu-like symptoms:
• Grows in Human Amnion/ Embryonic Lung Fibroblast cell
- fever, malaise, chills, fatigue,sore throat
• Type 1 - 24, NO TYPE: 15, 18, 23 (21 members)
• Self-limiting
Group B
• Type 1 - 6
2. Nonparalaytic Poliomyelitis / Aseptic Meningitis
• Flu-like symptoms + 2 common unique signs
A) stiffness PATHOGENESIS & PATHOLOGY
B) pain the back & neck • Recovered from the blood in the early stages of natural
• Individuals with good immune system is able to recover infections in humans
completely after 2-10 days of infection • Also found in the throat for a few days early in the infection
• Also found in stool for up to 5-6 weeks
3. Paralytic poliomyelitis - Enterovirus is always excreted in the stool
• Flaccid paralysis - reduced muscle tone (vegetative)
• Some experiences painful spasms in non-paralyzed muscle CLINICAL FINDING
1. Aseptic meningitis
4. Progressive Postpoliomyelitis Muscle Atrophy
• Caused by all types of Group B Coxsackieviruses and
• Occurs as RECRUDESCENCE of initial paralysis
Group A7, A9
- recurrence of paralytic poliomyelitis
- Groups B, A7, A9
- occurs decades after primary infection
• Manifestation: flu-like s/sx - fever, malaise, nausea,
• Individual has no viral infection
abdominal pain, some progress to mild muscle weakness
- happens because of physiological effect
• Patient may have complete recovery
A) Initial infection
B) Aging process
2. Herpangina
- results to muscular degeneration
• Severe form/ fibrile pharyngitis
-- lost of neuromuscular function
• All Grp A
• Frequently observed in small young children
LABORATORY DIAGNOSIS • Nothing to do with Herpesvirus
• Recovered from throat swab taken soon after the onset of • Manifestation: abrupt fever, sore throat, & vesicle on the
illnesses and from rectal swab/ stool sample collected over posterior half of the upper palate, pharynx, tonsils, gums
long periods of time (because it's shed continuously) • Self-limiting, completely healed
• Kept frozen during transit to the laboratory
• Cultures - Human or monkey cells 3. Hand-foot-and-mouth disease
• Cytopathogenic effect appear in 3- 6 days • Associated with oral & pharyngeal ulceration
• An isolated virus is identified and typed by neutralization with • Vesicular rash (palm, soles of feet), can spread (arms, legs)
specific antiserum - Vesicular lesions are equipped with virus
• No known permanent carrier • Heals without crust
• Long term excretion in stool - Unlike Herpes virus, which may leave crust
• Group A 16 & Group B1 Coxsackievirus
ADVANTAGES - Group A16, B1
Is there Immunity against Poliovirus?
4. Pleurodynia/Epidemic Myalgia
• Yes, it's permanent.
• Caused by all Group B
• Permanent Immunity is Antibody mediated.
• Manifestations: abrupt fever, stabbing pain in the chest w/
abdominal pain
HISTORY • Self-limiting
• 1988 - WHO created a program, "Global Eradication of
Poliovirus" 5. Myocarditis
• Done through mass/global vaccination • Serious inflammation/infection in the myocardium of the
• Eradication was achieved except for some portions including heart
the Philippines. • Fatal in neonates

VACCINES FOR POLIOVIRUS 6. Generalized disease of infants

• Extremely serious conditions associated with Group B
1. Sabin vaccine
Coxsackievirus
• Oral vaccine
• Neonates / infants has simultaneously viral infection which
• Problem: live attenuated virus/ vaccine is used
affects multiple organs (heart, liver, brain)
- inactivated, reduced virulence factor
• Not given to immunocompromised patients (young children,
elder, prior conditions)
- bec. live virus is used
RNA VIRUS: PICORNAVIRUS and REOVIRUS
Ley Andrea Arranz & Joeperl Verdadero

LABORATORY DIAGNOSIS PATHOGENESIS & PATHOLOGY

• Coxsackievirus has no vaccine & no anti-viral drug • Virus enters via the upper respiratory
• Treatment: Increased Immune system • Replication is limited to the surface epithelium of the nasal
• Clinical - s/sx are basis of the treatment mucosa

A. Recovery of Virus CLINICAL FINDINGS

• Specimen can be inoculated into tissue cultures and suckling
• Mild common colds
(baby) mice
- Acute form / Illness lasts up to 7 days
• Tissue culture - cytopathic effects appear within 5-14 days
• Self-limiting
• Suckling mice - signs of illness appear usually within 1-2
weeks
REOVIRUS
- very tedious, obsolete because of animal rights
Reoviridae
• dsRNA, naked, icosahedral symmetry
B. Nucleic Acid Detection
• PCR - Highly specific & sensitivity
MEMBERS
C. Serology • Orthoreovirus - mild URT illness, GIT ilIness, biliary atresia
• Serological assay • Orbivirus / Coltivirus - febrile illness associated with
headache and myalgia (zoonosis)
OTHER ENTEROVIRUSES • Rotavirus - GTI illness, respiratory tract illness (?)
Echoviruses - Respi Tract: Not proven
• Enteric Cytophatic Human Orphan Virus • Non-enveloped; double-layered protein capsids with
• Infects the enteric tract/GIT dsRNA genomes
• Can be recovered in mainly in stool and sometimes in throat - Double: outer, inner layers
• Can be grown in any tissue culture (not picky) • Highly Stable over wide pH & temperature changes & in
• Has >30 serotypes as of now and not all causes infection airborne aerosols

CLINICAL SIGNIFICANCE STRUCTURE

• Aseptic meningitis
• Encephalitis
• Febrile illness without rash (with rash)
• Common cold
• Ocular diseases

Enterovirus 70
• Main cause of Hemorrhagic Conjunctivitis (eye infection)
- blood clot in the eye
• Highly endemic in Africa / Southeast Asia

Enterovirus 71
• Important cause of meningitis, encephalitis, paralysis,
hand-foot-mouth diseases • Icosahedral with double stranded segmented genome
• Reovirus - 10 segments
Rhinoviruses • Rotavirus - 11 segments
• Mainly isolated from nasal secretions (throat / oral cavity) • (+) re assortment of gene segments --> create hybrid viruses
• Common cold virus (mutations)
• Most common recovered agents from people with mild upper
respiratory illnesses
• Human rhinoviruses can be divided into major & minor
receptor groups
- based on receptor genes
A) Major: Intercellular Adhesin Molecule 1 (ICAM 1)
B) Minor: Low Density Lipoprotein Receptor (LDL-R)

GENERAL PROPERTIES
• Unstable below at pH of 5.0 - 6.0
- completely inactivated at pH 3.0
• More thermostable than other enteroviruses
• Infectious only for humans, gibbons, chimpanzees
- Not to lower animal forms
• Most grow better at 33° C
- 33° C is the Optimal temperature, temperature in nasal area
• More than 150 serotypes are known
- reason why vaccine is hard to make
Reoviridae: Orthoreovirus
• Mammalian reovirus
• Ubiquitous: present in sewage & river water
• 3 serotypes (1, 2& 3) --> based on neutralization and
hemagglutination-inhibition tests
• Most people infected during childhood
• (+) antibodies in 75% of adults
- significant Antibody can be isolated
• No significant disease in humans
RNA VIRUS: PICORNAVIRUS and REOVIRUS
Ley Andrea Arranz & Joeperl Verdadero

MAIN PATHOLOGIC PROCESS • Shortening and blunting of microvilli; mononuclear cell

After ingestion & proteolytic production of ISVP --> infiltration into lamina propia (seen in biopsy)
binds to M cells in small intestines --> • 1010 viral particles/em of stool released during disease
transfer virus to lymphoid tissue of Peyer's patches --> maximal shedding 2-5 days after start of diarrhea
replicate --> (+) viremia (+ )Outbreaks in Pre-schools & Daycare

• Main receptor: M cells in Small Intestine

CLINICAL SYNDROMES
1. Usually asymptomatic
2. Common cold-like mild upper respiratory tract illness
3. Gastrointestinal disease
4. Biliary atresia

LABORATORY DIAGNOSIS
1. Assay of viral antigen or RNA in clinical material
2. Virus isolation
3. Serologic assays

Reoviridae: Rotavirus
• Rota - Wheel
• X-ray calligraphy: Wheel-like
• Most Common Agents of Infantile diarrhea (world wide) CLINICAL SYNDROMES
• Ubiquitous worldwide
• 95% of children infected by 3-5 years old • Incubation Period = 48 hrs
• Stable at: • self-limited
a) room temperature • vomiting diarrhea, fever, dehydration
b) treatment with detergents • (-) fecal leukocyte & blood
c) pH 3.5-10 May be Highly Fatal in infants from developing countries & who
d) repeated freezing & thawing are malnourished & dehydrated before the infection
e) survives on fomites
LABORATORY DIAGNOSIS
DIVIDED INTO 1. Direct Detection of Viral Antigens in Stool
1. Serotypes - based primarily on the VP7 outer capsid - METHOD OF CHOICE
protein 2. Enzyme immunoassay
2. Groups - based on antigenicity of VP6 & electrophoretic 3. Latex agglutination
mobility of genomic segments A to G 4. Serology
- Group A is the only one that produces Human - four fold increase in antibody titer
infections/diseases - released after viral infection

PATHOGENESIS
• MOT fecal - oral, possibly respiratory route
• Adsorption to columnar epithelial cells covering villi of SI -->
release of NSP4 protein -->
cytolytic & toxin-like activity -->
results to (A) loss of electrolytes
(B) prevention of water re-absorption -->
common manifestation: water diarrhea -->
leads severe dehydration
• NSP4 protein promotes
1. calcium influx into enterocytes
- leads to electrolyte imbalance
- improper water re-absorption
2. release of neuronal activators
3. neuronal alteration in water absorption