RNA Non Enveloped Viruses

8/3/2019 RNA Non Enveloped Viruses

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RNA NonenvelopedRNA NonenvelopedVirusesViruses

PICORNAVIRUSESPICORNAVIRUSES

CALICIVIRUSESCALICIVIRUSES

REOVIRUSESREOVIRUSES


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1- PICORNAVIRUSES1- PICORNAVIRUSES

small (20-30 nm) nonenveloped,small (20-30 nm) nonenveloped,

icosahedral, +ve ssRNA virusesicosahedral, +ve ssRNA viruses

Replicate in the cytoplasmReplicate in the cytoplasm

resist lipid solvents (e.g. ether)resist lipid solvents (e.g. ether)

The family includes 2 groups:The family includes 2 groups:

1- Enteroviruses1- Enteroviruses

2- Rhinoviruses2- Rhinoviruses


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Human hepatitis

virus A

Hepatovirus

Disease of the

nasopharyngeal

region (e.g.common coldvirus)

Rhinovirus

Diseases of thehuman (and other)

alimentary tract(e.g. polio virus)

EnterovirusPolioCoxsackie A and BEchoOther enteroviruses

Genera that infect humans

Genera of Picornaviruses


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gutoro-fecal

72Resistant

37degrees C(appro

x)

resistantto acidpH

Enterovirus

es

upperrespiratorytract

aerosol>100

33degrees C(approx)

labile toacid pH

Rhinoviruses

Site ofprimaryinfection

Transmission

Serotypes

Detergentsensitivity

Optimumgrowthtemperature

pHsensitivity

Properties of Rhino- and Entero-viruses


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ENTEROVIRUSESENTEROVIRUSES

68 - 71

Other

Enteroviruses

Enterovirus 72

Hepatitis A

1 - 9, 11 - 27, 29- 34Echovirus

1 - 6Coxsackie B

1 - 22, 24Coxsackie A1 - 3Polio

SerotypesVirus family

Enteroviruses


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PoliovirusPoliovirus

Important Properties:Important Properties:

- Infection is limited to the primates (receptor?)- Infection is limited to the primates (receptor?)

- Three serologic types are present- Three serologic types are present

-- CD155, the polio virus receptor, is expressedCD155, the polio virus receptor, is expressed (in spinal(in spinal

cord anterior horn cells, dorsal root ganglia, skeletal muscle, motorcord anterior horn cells, dorsal root ganglia, skeletal muscle, motor

neurons and some cells of the lymphoid system)neurons and some cells of the lymphoid system)

-- For unknown reasons, polio virus does not spread toFor unknown reasons, polio virus does not spread to

the cells of the central nervous system in all patientsthe cells of the central nervous system in all patients
http://pathmicro.med.sc.edu/lecture/polio.jpg


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Replication CycleReplication Cycle

Interaction of the virus with its receptorInteraction of the virus with its receptor

Enters the cell, uncoatingEnters the cell, uncoating

The genome RNA functions as mRNAThe genome RNA functions as mRNA

Translated into one very large polypeptideTranslated into one very large polypeptide

viral RNA polymerase synthesized the progenyviral RNA polymerase synthesized the progeny

RNA genomesRNA genomes

ReplicationReplication (+ve ssRNA::-ve ssRNA:: +ve ssRNA)(+ve ssRNA::-ve ssRNA:: +ve ssRNA)

Assembly occurs at the cytoplasmAssembly occurs at the cytoplasm

Release occurs by lysis of the cellsRelease occurs by lysis of the cells


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Transmission & EpidemiologyTransmission & Epidemiology

Poliovirus is spread via the fecal-oral routePoliovirus is spread via the fecal-oral route

Most disease results from type 1 polio virusMost disease results from type 1 polio virus

Poliovirus caused about 21, 000 cases of paralyticPoliovirus caused about 21, 000 cases of paralyticpoliomyelitis in the United States each year in thepoliomyelitis in the United States each year in the1940's - 50's1940's - 50's

Today, the number of cases of paralytic polio in theToday, the number of cases of paralytic polio in theUS is fewer than 10 and these are the result of theUS is fewer than 10 and these are the result of theattenuated (Sabin) vaccine reverting to virulenceattenuated (Sabin) vaccine reverting to virulence


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Pathogenesis & ImmunityPathogenesis & Immunity

Replicate 1st in oropharynx & GIReplicate 1st in oropharynx & GI

Then, spread via blood to the CNSThen, spread via blood to the CNS

The virus replicates in theThe virus replicates in the motor neuronsmotor neurons

located in thelocated in the anterior hornanterior horn of the spinal cordof the spinal cord

Paralysis occurs due to the death of these cellsParalysis occurs due to the death of these cells

Immunity is lifelongImmunity is lifelong type-specifictype-specific


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Clinical FindingsClinical Findings

Asymptomatic polio infection:Asymptomatic polio infection:

-- This occurs when the replication of the virus is restricted toThis occurs when the replication of the virus is restricted to

the GI tractthe GI tract

- IP is 10-14 days- IP is 10-14 days

Abortive poliomyelitis (minor illness):Abortive poliomyelitis (minor illness):

- i- is febrile disease and occurs in the first week of infections febrile disease and occurs in the first week of infection

-- occurs in about 5% of infected individualsoccurs in about 5% of infected individuals

-- general malaise which may be accompanied by vomiting, ageneral malaise which may be accompanied by vomiting, a

headache and sore throatheadache and sore throat


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Clinical Findings Cont.Clinical Findings Cont.

Non-paralytic poliomyelitis:Non-paralytic poliomyelitis:

-- TThis is similar tohis is similar to aseptic meningitisaseptic meningitis with fever, headache &with fever, headache &a stiff necka stiff neck

Paralytic polio:Paralytic polio: -- flaccid paralysisflaccid paralysis is the predominant findingis the predominant finding

- Respiratory paralysis can occurs due to brain stem- Respiratory paralysis can occurs due to brain steminvolvmentinvolvment

Post-polio syndrome:Post-polio syndrome:

- Occurs many years after the acute illness- Occurs many years after the acute illness-- involves further loss of function in affected muscles perhapsinvolves further loss of function in affected muscles perhaps

as a result of further neuron loss.as a result of further neuron loss.


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Laboratory DiagnosisLaboratory Diagnosis

Isolation of the virusIsolation of the virus

Detection a rise in antibody titerDetection a rise in antibody titer

Clinical spicemens include: throat swabs,Clinical spicemens include: throat swabs,

stool or spinal fluidstool or spinal fluid


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Treatment & PreventionTreatment & Prevention

No antiviral therapyNo antiviral therapy

Prevented by vaccination using:Prevented by vaccination using:

1- killed vaccine (1- killed vaccine (Salk vaccineSalk vaccine,,

inactivated vaccine,inactivated vaccine, IPVIPV))

2- live attenuated vaccine (2- live attenuated vaccine (SabinSabinvaccinevaccine, oral vaccine,, oral vaccine, OPVOPV))

(current version of IPV is called enhanced(current version of IPV is called enhanced

polio vaccinepolio vaccine eIPVeIPV))
http://pathmicro.med.sc.edu/virol/coxsackb.gif


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CoxsackievirusesCoxsackieviruses

TThere are many infections caused by Coxsackiehere are many infections caused by Coxsackie

viruses, most of which are never diagnosed preciselyviruses, most of which are never diagnosed precisely

Coxsackie type ACoxsackie type A usually is associated with surfaceusually is associated with surfacerashes (exanthems)rashes (exanthems)

Type BType B typically causes internal symptomstypically causes internal symptoms

(pleurodynia, myocarditis)(pleurodynia, myocarditis)

Both can also cause paralytic disease or mildBoth can also cause paralytic disease or mild

respiratory tract infection.respiratory tract infection.
http://pathmicro.med.sc.edu/virol/coxsackb.gif


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Meningitis:Meningitis:

-- Enteroviruses are the major cause of viralEnteroviruses are the major cause of viral

meningitismeningitis

- B- Both Coxsackie virus A and B can cause asepticoth Coxsackie virus A and B can cause asepticmeningitismeningitis

-- Viral meningitis typically involves a headache, stiffViral meningitis typically involves a headache, stiff

neck, fever and general malaiseneck, fever and general malaise-- Most patients recover from the disease unlessMost patients recover from the disease unless

encephalitis occursencephalitis occurs

-- The disease is most prevalent in the summer and fallThe disease is most prevalent in the summer and fall


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Herpangina:Herpangina:

-- Coxsackie virus ACoxsackie virus A can cause a fever with painfulcan cause a fever with painfululcers on the palate and tongue leading toulcers on the palate and tongue leading toproblems swallowing and vomitingproblems swallowing and vomiting

-- Treatment of the symptoms is all that is requiredTreatment of the symptoms is all that is required

as the disease subsides in a few days.as the disease subsides in a few days.


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Hand, foot and mouth diseaseHand, foot and mouth disease: (HFMD): (HFMD)-- This is an exanthem (rash) caused byThis is an exanthem (rash) caused by Coxsackie typeCoxsackie typeA16A16

--

Symptoms include fever and blisters on the hands,Symptoms include fever and blisters on the hands,

palate and feet.palate and feet.

-- it subsides in a few daysit subsides in a few days

Myocarditis:Myocarditis:-- Type A and BType A and B can cause myocarditis in neonates andcan cause myocarditis in neonates andyoung childrenyoung children

- Fever, chest pains, arrhythmia and even cardiac- Fever, chest pains, arrhythmia and even cardiacfailure can resultfailure can result

-- Mortality rates are high.Mortality rates are high.


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EchovirusesEchoviruses

ECHO =ECHO = eentericnteric ccytopathicytopathic hhumanuman oorphanrphan

Cause aseptic meningitis, URT, febrile illness,Cause aseptic meningitis, URT, febrile illness,

infantile diarrhea &infantile diarrhea & hemorrhagic conjunctivitishemorrhagic conjunctivitis

Transmitted by fecal-oral routeTransmitted by fecal-oral route

Diagnosed by isolation in cell cultureDiagnosed by isolation in cell culture

No vaccine or antiviral availableNo vaccine or antiviral available


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Other enterovirus diseasesOther enterovirus diseases

Acute hemorrhagic conjunctivitisAcute hemorrhagic conjunctivitis isis

caused bycaused by Coxsackie A24Coxsackie A24 andand EnterovirusEnterovirus

70.70. The disease resolves in a week or twoThe disease resolves in a week or two

Enterovirus 71Enterovirus 71 is one of the leadingis one of the leading

causes ofcauses ofviral CNS diseaseviral CNS disease, including, including

meningitis, encephalitis, & paralysismeningitis, encephalitis, & paralysis

Enterovirus 72 is hepatitis A virusEnterovirus 72 is hepatitis A virus


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RHINOVIRUSESRHINOVIRUSES

Rhinoviruses are the main cause of theRhinoviruses are the main cause of thecommon coldcommon cold

There are more than 100 serotypesThere are more than 100 serotypes

They areThey are sensitive to low pHsensitive to low pH andand replicatereplicatewell at 33well at 33 CC

Infect the URT & spread directly viaInfect the URT & spread directly viaaerosolsaerosols or byor by fomitesfomites such as hands andsuch as hands and

other forms of direct contactother forms of direct contact
http://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Search&query=fomitehttp://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Search&query=fomitehttp://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Search&query=fomite


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RHINOVIRUS DISEASERHINOVIRUS DISEASE

There are nearlyThere are nearly 62 million cases62 million cases of theof thecommon cold annually in the UScommon cold annually in the US

52.2 million52.2 million of these cases affect Americansof these cases affect Americansunderunderage 17age 17

There are nearlyThere are nearly 22 million22 million school-loss daysschool-loss days

annually due to the common coldannually due to the common cold

There are approximatelyThere are approximately 45 million bed45 million bed daysdaysannually associated with the common coldannually associated with the common cold


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IP isIP is 2-42-4 daysdays

Symptoms includeSymptoms include discharging or blockeddischarging or blocked

nasal passages often accompanied bynasal passages often accompanied bysneezes, and perhaps a sore throatsneezes, and perhaps a sore throat

The illness lasts about 1 weekThe illness lasts about 1 week

other viruses cause symptoms that areother viruses cause symptoms that are

similar to those of rhinovirusessimilar to those of rhinoviruses

(parainfluenzaviruses, coronaviruses and enteroviruses)(parainfluenzaviruses, coronaviruses and enteroviruses)


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There is usually no need to treat the infectionThere is usually no need to treat the infection

ButBut rehydration and keeping the airwaysrehydration and keeping the airways

unblocked is advisableunblocked is advisable Prescription of aspirin to relive feverPrescription of aspirin to relive fever????

Interferon nasal sprays have little effectInterferon nasal sprays have little effect

The best way to avoid spreading the virusThe best way to avoid spreading the virus

is interrupt the infection chain by handis interrupt the infection chain by hand

washingwashing


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2- CALICIVIRUSES2- CALICIVIRUSES

They are almost like PicornavirusesThey are almost like Picornaviruses

But differ in having:But differ in having:

1- larger genome1- larger genome2- having distinctive spikes on the2- having distinctive spikes on the

surfacesurface

Two human pathogens in this family:Two human pathogens in this family:

1- Norwalk virus (norovirus)1- Norwalk virus (norovirus)

2- Hepatitis E virus2- Hepatitis E virus


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Norwalk virus (Norovirus)Norwalk virus (Norovirus)

One of the most common causes ofOne of the most common causes of

viral gastroenteritis in adultsviral gastroenteritis in adults

It is named after anIt is named after an outbreakoutbreak (Ohio,(Ohio,1969)1969)

It hasIt has +ve ssRNA+ve ssRNA, nonenveloped,, nonenveloped,

icosahedralicosahedral Uncertain serotypesUncertain serotypes

Replicative cycle is unclear but similarReplicative cycle is unclear but similar

to Picornavirusesto Picornaviruses


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Fecal-oral (Fecal-oral (seafoodseafood & water)& water)

Person-to-person (group settings)Person-to-person (group settings)

Outbreaks inOutbreaks in cruise shipscruise ships, schools,, schools,campscamps

Low infectious dose, resistance toLow infectious dose, resistance tochlorination & drying, are factorschlorination & drying, are factorsenhancing the infectionenhancing the infection


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Pathogenesis & ImmunityPathogenesis & Immunity

Infection is limited to the mucosal cells of GIInfection is limited to the mucosal cells of GI

Watery diarrheaWatery diarrhea W/O bloodW/O blood

Mostly asymptomaticMostly asymptomatic

Short immunity (reinfection)Short immunity (reinfection)


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Sudden onset ofSudden onset ofvomiting & diarrheavomiting & diarrhea

WithWith low-grade feverlow-grade fever&& abdominalabdominal

crampscramps

ButBut W/O bloodW/O blood

It lasts for several daysIt lasts for several days


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Diagnosed clinically and rarly by PCRDiagnosed clinically and rarly by PCR

NoNo antiviral drugs or vaccineantiviral drugs or vaccine

But IV fluid may requiredBut IV fluid may required

Personal hygienePersonal hygiene


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3- REOVIRUSES3- REOVIRUSES

REO =REO = RRespiratoryespiratory EEntericnteric OOrphanrphan

RotavirusesRotaviruses is the most importantis the most important

human pathogen in this familyhuman pathogen in this family

TheThe most commonmost common cause of viralcause of viral

gastroenteritis ingastroenteritis in young childrenyoung children


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Important PropertiesImportant Properties

Segmented dsRNA, 2-layer icosahedralSegmented dsRNA, 2-layer icosahedral

Contains RNA-dependent RNAContains RNA-dependent RNA

polymerasepolymerase

Infect many domestic animals (human?)Infect many domestic animals (human?)

Six human serotypesSix human serotypes


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ReplicationReplication

Attachment (Attachment (-adrenergic receptor-adrenergic receptor))

EntryEntry

Synthesis ofSynthesis ofmRNAmRNA (10-11 segments)(10-11 segments)

Translation to structural & nonstructural proteinsTranslation to structural & nonstructural proteins

RNA-polymeraseRNA-polymerase synthesizes strand, then thesynthesizes strand, then the

+strand synthesize+strand synthesize

Released by lysisReleased by lysis


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Fecal-oral routeFecal-oral route

Pathogenesis & Immunity- Replication in mucosal cells of small intestine

cause excess secretions of fluids & electrolytes

- No inflammation, no bloody diarrhea

- IgA is protective (serospecific)


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Laboratory DiagnosisLaboratory Diagnosis

RIA or ELISA (stool)RIA or ELISA (stool)

Immunoelectron microscopyImmunoelectron microscopy

4-fold increase in Abs titer4-fold increase in Abs titer


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NoNo antivral therapy, no vaccineantivral therapy, no vaccine

Hygienic measures like:Hygienic measures like:

- proper sewage disposal- proper sewage disposal

- hand washing- hand washing

are helpfulare helpful

Documents

RNA Non Enveloped Viruses