8. Picorna Viruses

7/27/2019 8. Picorna Viruses

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PICORNAVIRUSES

(Enterovirus & Rhinovirus groups)


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IntroductionPicornaviruses a very large virus family with respect to thenumber of members

But smallest in terms of virion size and complexity.

Enteroviruses are transient inhabitants of humanalimentary tract

May be isolated from throat or lower intestine.

Rhinoviruses are isolated from nose and throat


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Introduction contd Replication occur in cytoplasm of host cells Cause diseases in humans ranging from severe paralysis to

aseptic meningitisPleurodynia ( Bornholm Disease), myocarditis, vesicular andexanthematous skin lesions,

Mucocutaneous lesions, respiratory illnesses,

Undifferentiated febrile illness, conjunctivitis and severegeneralized disease of infant


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Properties & Classification of

Picornaviruses Virion is having icosahedral symmetry, 24-30nm.

It contain single stranded positive sense RNA. There is noenvelopeContains six genera:

Enterovirus (enteroviruses)Rhinovirus(rhinoviruses)Hepatovirus (hepatitis A virus)

Parechovirus (parechoviruses), Aphthovirus (foot-and-mouth disease viruses)Cardiovirus (Cardioviruses)

The first four groups contain important humanpathogens.


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Enteroviruses Group


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EnterovirusesEnteroviruses are a genus of the picornavirus family which replicatemainly in the gutSingle stranded naked RNA virus with icosahedral symmetry

Unlike rhinoviruses, they are stable in acid pHCapsid has 60 copies each of 4 proteins, VP1, VP2, VP3 and VP4arranged with icosahedral symmetry around a positive sense genome.

At least 72 serotypes are known: divided into 5 groups

Polioviruses

Coxsackie A viruses

Coxsackie B viruses

Echoviruses type

Enteroviruses (more recently, new enteroviruses subtype have been allocatedsequential numbers (68-72))


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Enterovirus Particles

Courtesy of Linda M. Stannard, University of Cape Town, S.A.h


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Properties of EnterovirusesCPE in cell cultures

Monkey Human cell Pathology inGroup Virus types kidney culture newborn mice Major disease associations

Poliovirus 3 types + + - Paralytic poliomyelitis, aseptic(1 - 3) meningitis, febrile illness.

Coxsackie 23 types - or I - or I + Aseptic meningitis, herpangina,group A (A1-22, A24) febrile illness, conjunctivitis

(A24), hand, foot and mouth disease.

Coxsackie 6 types + + + Aseptic meningitis, severe neonatalgroup B (B1-6) disease, myopericarditis, Bornholm

disease, encephalitis, febrileillness.

Echovirus 31 types + E - Aseptic meningitis, rash, febrile(1-9, 11-27 illness, conjunctivitis, severe

29-33) generalized neonatal disease.

Enterovirus 5 types + + - Polio-like illness, aseptic(68-72) meningitis, hand, foot and mouth

(E71), epidemic conjunctivitis (E70)hepatitis A (E72)


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PoliovirusThree serotypes of poliovirus (1, 2, and 3) but no commonantigen.

Have identical physical properties but only share 36-52%nucleotide homology.

Humans are the only susceptible hosts

Polioviruses are distributed globally

The availability of immunization and the polioviruseradication campaign has eradicated poliovirus in mostregions of the world except in the Indian Subcontinent andAfrica.


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PathogenesisThe incubation period is usually 7 - 14 days.

Following ingestion, the virus multiplies in the oropharyngeal andintestinal mucosa.

The lymphatic system, in particular the tonsils and the Peyer's patches of the ileum are invaded and the virus enters the bloodresulting in a transient viraemia

In a minority of cases,the virus may involve the CNS followingdissemination.


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Clinical ManifestationsThere are 3 possible outcomes of infection:

Subclinical infection (90 - 95%) - inapparent subclinical infection account for thevast majority of poliovirus infections

Abortive infection (4 - 8%) - a minor influenza-like illness occurs, recoveryoccurs within a few days and the diagnosis can only be made by the laboratory

The minor illness may be accompanied by aseptic meningitisMajor illness (1 - 2%) (poliomyelitis) - the major illness may present 2 - 3 daysfollowing the minor illness or without any preceding minor illness.

Signs of aseptic meningitis are common. Involvement of the anterior horncells lead to flaccid paralysis .

Involvement of the medulla may lead to respiratory paralysis and death.


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Epidemiology Children are most susceptible

Humans are only reservoir of infection

Crowded conditions, poor hygiene and sanitation favorsthe transmission

It is mainly transmitted by contaminated water withdrinking water


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Prevention contd.. No specific antiviral therapy is availableHowever, the disease may be prevented throughvaccination

There are two vaccines availableIntramuscular Poliovirus Vaccine (IPV)

Consists of formalin inactivated virus of all 3 poliovirus

serotypesProduces serum antibodies only: does not induce localimmunity and thus will not prevent local infection of the gutHowever, it will prevent paralytic poliomyelitis sinceviraemia is essential for the pathogenesis of the disease.


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Prevention contd.. Oral Poliovirus Vaccine (OPV)

Consists of live attenuated virus of all 3 serotypesProduces local immunity through the induction of an IgA response as well as systemic immunity.Rarely causes paralytic poliomyelitis, around 1 in 3

million doses.


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Prevention contd. Most countries use OPV because of its ability to inducelocal immunity

The normal response rate to OPV is close to 100%.

OPV is used for the WHO poliovirus eradication campaign.

Poliovirus was targeted for eradication by the WHO by theend of year 2000


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CoxsackievirusesCoxsackieviruses are distinguished from other enteroviruses by their pathogenicityfor suckling rather than adult mice

They are divided into 2 groups on the basis of the lesions observed in sucklingmice.

Group A produce a variety of illness like herpangina (vesicular pharyngitis),hand-foot-and-mouth disease and acute hemorrhagic conjunctivitis.

Group B causes pleurodynia (epidemic myalgia), myocarditis, pericarditis,meningoencephalitis and severe generalized disease of children

Group A and B may also cause aseptic meningitis, respiratory andundifferentiated febrile illnesses, hepatitis and paralysis

Paralysis produced by non polioviruses is incomplete and reversible

Coxsackie B viruses are most commonly identified agents of viral heart

disease


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Laboratory diagnosisVirus can be isolated form throat washings, stool, nasalsecretions. In aseptic meningitis, CSFIn hemorrhagic conjunctivitis virus is isolated from conjunctivalswabsSamples are inoculated in tissue cultures and also in suckling

mice.Tissue culture show CPE after 5-14 days.

Suckling mice show signs of illness appear within 3-8 days(group A) and 5-14 days (group B).Serologic diagnosis can be done by Neutralization ,immunofluorescence technique


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Epidemiology It is encountered all round the world

Isolations made from human feces, pharyngeal swabs, sewageand flies

Familial exposure is important in acquiring the infection .Control :

No vaccine or antiviral drugs are available


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EchovirusesThe first echoviruses were accidentally discovered in human faeces,unassociated with human disease during epidemiological studies of

polioviruses.

The viruses were named echoviruses ( Enteric, Cytopathic, Human,Orphan viruses).

These viruses were produced CPE in cell cultures, but did not inducedetectable pathological lesions in suckling mice.

Altogether, there are 32 echoviruses (types 1-34; echovirus 10 and 28 were found to be other viruses and thus the numbers are unused)

There is no group echovirus Ag but heterotypic cross-reactions occur between a few pairs.


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New Enteroviruses Newly identified picornaviruses that are not polioviruses

No longer classified separated into the species coxsackie andechovirus because of the ambiguities presented by overlapping host

range variations.

Four new enteroviruses have been identified (68 - 72).

Enterovirus 70 is the causative agent epidemics of acute

haemorrhagic conjunctivitis

That swept through Africa, Asia, India and Europe from 1969 to1974. The virus is occasionally neurovirulent.


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New Enteroviruses contd Enterovirus 71 appears to be highly pathogenic

Associated with epidemics of a variety of acute diseases

Aseptic meningitis, encephalitis, paralytic poliomyelitis-likedisease and hand-foot-mouth disease.

Enterovirus 72 was originally assigned to hepatitis Avirus,

But it had now been assigned to a new family calledheptoviruses


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Diseases summary with EnterovirusesSyndrome Polio Cox A Cox B EchoParalytic disease + + + +Meningitis-encephalitis + + + +Carditis + + + +Neonatal disease - - + +Pleurodynia - - + -Herpangina - + - -Rash disease - + + +Haemorr. conjunctivitis - + - -

Respiratory infections + + + +Undifferentiated fever + + + +Diabetes/pancreatitis - - + -


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Laboratory DiagnosisVirus Isolation

Mainstay of diagnosis of enterovirus infectionCoxsackie B and Echoviruses can be readily grown in cell culture fromthroat swabs, faeces, and rectal swabs. They can also be isolated from theCSFCoxsackie A viruses cannot be easily isolated in cell culture.

Molecular techniques may provide a better alternative

SerologyVery rarely used for diagnosis since cell culture is efficient.

Neutralization tests or EIAs are used but are very cumbersome and thusnot offered by most diagnostic laboratories


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Cytopathic Effect

(Virology Laboratory, New-Yale Haven Hospital)


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Treatment and PreventionThere is no specific antiviral therapy available against enterovirusesother than polio.

Some authorities use IVIG (Immune globulin) in the treatment of neonatal infections or severe infections in immunocompromisedindividuals. However, the efficacy is uncertain.

HNIG (Human normal immunoglobulin) have been to preventoutbreaks of neonatal infection with good results.

There is no vaccine available mainly because of the multiplicity of serotypes. There is little interest in developing a vaccine except againstenterovirus 71 and coxsackie B viruses.


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RHINOVIRUS GROUP


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RHINOVIRUSThey are called common cold viruses

They are commonly isolated from mild upper respiratoryillnesses

They are usually isolated form nasal secretions, throat andoral secretions.


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Characteristics of RhinovirusThese are picornaviruses similar to enteroviruses

But differ from them in having acid lability

Thermostable than enteroviruses and survive for days

Animal susceptibility and growth

These are infectious to humans and some primates

They grow in human cell lines like WI-38 and MRC-5 lines

Antigenic properties

More than 100 serotypes are known


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Pathogenesis and pathology Virus enters via upper respiratory tract

High titers of virus in nasal secretions are found after 2-4days of infection

After that virus titer falls but illness persists

Replication is limited to surface epithelium of nasal mucosa

It may lead to edema and mild cellular infiltration

Nasal secretion increases in quantity and in proteinconcentration

It may occasionally infect lower respiratory tract


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Clinical features Acute illness last for 7 days

A non productive cough may persist for 2-3 weeks

Usual symptoms in adults are sneezing, nasal obstruction,nasal discharge,

Sore throat, mild cough, head ache, malaise and chillysensation, little or no fever

Nasal and nasopharyngeal mucosa become red and swollen

Secondary bacterial infections may occur leading to otitismedia, sinusitis, bronchitis or pneumonitis in children.


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EpidemiologyIt occur throughout the world

Prevalence is lower in summer

Virus is transmitted by close contact

The fingers of a person with a cold and transmitted toothers

By hand to hand

Hand to object to hand contamination.

Self inoculation after hand contamination is the main modeof spread

Infection rate is higher in infants, children


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Treatment & controlNo specific prevention method or treatment is available

It is difficult to develop a vaccine because of multiplicity of

serotypes of rhinoviruses


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CORONAVIRUSES


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Properties of CoronavirusesLarge 80 to 220nm, spherical,enveloped RNA viruses

There are 20nm long petal shapedprojections (spikes) on the outer surface

of the envelope like a solar coronaThe spikes are made up of glycoproteins

They cause common colds,gastroenteritis in infants.

These viruses are difficult to culture.

They show high frequency of recombination

SARS Severe acute respiratorysyndrome is associated with this virus

Replication: takes place in cytoplasm of

cell Genome consists of the longest known,


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PathogenesisCoronaviruses infect humans and other animals

In humans, the infections limited to upper respiratorytract restricted to the ciliated epithelia of the nose andtrachea

Responsible for about 30% of common cold infections

The infection may lead to patchy destruction of ciliatedepithelial cells and the loss of beating cilia

It may cause gastroenteritis


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Pathogenesis contd The SARS virus is transmitted aerogenically

An incubation time of two to 10 days

Clinically, fever and a marked shortness of breath is noted


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Clinical features:Respiratory disease:They cause common colds with afebrile, in adults

The symptoms are similar to rhinoviruses typically with nasaldischarge and malaiseIncubation period is 2 to 5 days

Lower respiratory infection with pneumonia is also common

SARS is a recent syndrome caused by this virus which ischaracterized by atypical pneumonia

Gastrointestinal Disease:Coronavirus like particles have been observed in feces of patientswith enteritis


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Laboratory diagnosis:Isolation and identification of virus:

It is very difficult to culture.

Direct examination:The antigens in cells in respiratory secretions may be detected byELISA.Electron microscopy (EM) and PCR can be used to detectcoronavirus particles in feces

Serology:Serodiagnosis using acute and convalescent sera is the main methodof confirmation of coronavirus infectionsELISA and haemagglutination tests can be used


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Epidemiology

They are major cause of respiratory illness in adults duringwinter months

When rhinovirus and other respiratory virus infections are low

They have found world wide.

SARS patients should be quarantined.


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Treatment and preventionThe only preventive measure to date isexposure prevention


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REOVIRIDAE


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REOVIRIDAEThe name reovirus is derived from the abbreviation forrespiratory enteric orphan virus

No diseases were associated with the virus upon its discovery(hence orphan virus)

This family consists of

Reoviruses: they are not known to cause any human disease

Rotavirus

Coltiviruses causes Colorado tick fever


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General characteristics Reoviruses and Rotavirus are 60-80nm with doublestranded segmented RNA genome

Capsid is composed of two layered shellsThe capsid is like wheel (rota means wheel)

The virion is icosahedral in symmetry without envelope

The family includes human rotaviruses, the most importantcause of infantile gastroenteritis around the world

Replication occurs in cytoplasm of host cell


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RotavirusesIt causes infantile diarrhea and sometimes in adults

Ranks sixth among the worlds global killers

Antigenic properties of rotaviruses:There are three major subgroups and nine serotypes exists.

Outer capsid protein are important antigens

Rotaviruses associated with human gastroenteritis are classified as

group A rotaviruses.But antigenically distinct rotaviruses have also caused diarrhealoutbreaks in adults

Cell culture :

They are fastidious agents to culture


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Pathogenesis:Rotaviruses infect cells in villi of small intestineThey multiply in cytoplasm of enterocytes and damagetheir transport mechanisms

A Rotavirus encoded protein may act as viral enterotoxin and induces secretion by triggering signal transductionpathwayDamaged cells slough into lumen of intestine and release

large quantities of virus in the stool Viral excretion may last up to 2 12 daysIt may be prolonged in malnourished patientsDiarrhea is due to impaired sodium and glucoseabsorption


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Clinical featuresIncubation period is 1 to 4 days

Typical symptoms include diarrhea, fever, abdominal pain,vomiting leading to dehydration

In infants and children, severe loss of electrolytes and fluidsmay be fatal unless treated

Asymptomatic infections may occur

Common source of infection is contact with pediatric casesEpidemics in adults have occurred.

Group B rotaviruses are associated with some outbreaks of diarrhea in adult patients in some countries.


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Laboratory diagnosisDemonstration of virus in stool collected in early in illnessand on a rise in antibody titer

Virus can be observed by IEM (immune electronmicroscopy), immunodiffusion, ELISA or PCR

Antibody titer rise can be detected by ELISA.


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EpidemiologyRotavirus infections predominate during winter seasons

80% of the population have antibody against rotavirus by

the age of 3Symptomatic infections are most common in childrenbetween 6 months and 2 years

Transmission is by fecal-oral route

Nosocomial infections are frequent.

Annual Rotavirus diarrhea deaths in the world


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( Much greater in developing countries)


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Treatment & Control:It is supportive, to correct the loss of water and electrolytesthat may lead to dehydration, acidosis, shock and death

Management consists of replacement of fluids andrestoration of electrolyte balance

Either intravenously or orally

Live attenuated vaccines now available for use in children


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Norwalk virus


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Norwalk Virus Norwalk genus name for original Norwalk virus and

other Norwalk-like viruses. Family Calicivirus

Calicivirae found worldwide, infecting humans, primates,and cattle, among others.

Increasingly being recognized as leading cause of foodborne illness.

Occur frequently at institutional settings, Schools, nursing homes.Restaurants, dorms.

Crowded quarters and poor hygiene contribute to its spread.


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Properties

Nonenveloped capsid/nucleocapsid. Icosahedral, 35-39 nm diameter and positive sense RNA Virus has four serotypes


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Mode of transmission The virus found in stool and vomit of infected.

Very infectious few virus particles needed to start largeoutbreak.

Primarily fecal-oral. Vomit airborne particles,capable of covering large radius

Very contagious infection via eating contaminated food

Contact with sick individual or contaminated surfaces


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Clinical features Acute gastroenteritis.

Illness begins suddenly, from 12-48 hours after ingestion.

Brief illness period.

Very young, elderly, and those with weakened immunesystems may experience more severe symptoms.

Infectiousness may last up to 2 weeks, no evidence of long-term carriers

Antibody developed has a protective role for short term againstreinfection with the same virus


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Diagnosis

Electron Microscope

RT-PCR

ELISA

Calicivirus is not easily studied

No efficient techniques have been developed to culture it ina lab setting.


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Treatment and Prevention Treatment is symptomatic

Effective hand washing, careful processing of food is importantto prevent food borne outbreaks

Purification of drinking water decreases outbreaks


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AstrovirusesSmall RNA viruses, ss +, none- enveloped, named becauseof star-shaped surface morphology, 28 nm in diameter.

Associated with cases of endemic gastroenteritis, usually inyoung children and neonatesCan cause occasional outbreaks.

Responsible for up to 10% of cases of gastroenteritis.

Similar disease to rota and adenoviruses.

Most people have antibodies by the age of three

Diagnosed by electron microscopy only, often very difficultbecause of small size.

8. Picorna Viruses

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