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Introduction to AdenovirusesIntroduction to Adenoviruses

Hugh FackrellHugh Fackrell

University of WindsorUniversity of Windsor

Windsor, ON CanadaWindsor, ON Canada

Fackrel@uwindsor.caFackrel@uwindsor.ca

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Adenoviruses OutlineAdenoviruses Outline

General Properties of AdenovirusGeneral Properties of AdenovirusClinical DiseasesClinical DiseasesTransmissionTransmissionDiagnosisDiagnosisPrevention and ControlPrevention and Control

Baron’s Web Site

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Adenovirus StructureAdenovirus Structure

isocahedral - 70-100 nmisocahedral - 70-100 nm252 capsomers252 capsomers

240 hexons240 hexons 12 fibrillar pentons12 fibrillar pentons

dsDNA lineardsDNA linear2 major core proteins2 major core proteins

2 minor proteins2 minor proteins

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Adenovirus Core ProteinsAdenovirus Core Proteins

Protein V- histone likeProtein V- histone likeProtein VII -bridge to capsidProtein VII -bridge to capsidProtein mu-??Protein mu-??Terminal ProteinTerminal Protein

covalently linked to DNAcovalently linked to DNA circularizes DNAcircularizes DNA primer for DNA replicationprimer for DNA replication

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Model of AdenovirusModel of Adenovirus

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Adenovirus virionsAdenovirus virions

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Adenovirus replicationAdenovirus replication

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Adenovirus mRNAAdenovirus mRNA

Adeno DNA reaches nucleusAdeno DNA reaches nucleus terminal protein binds to host DNAterminal protein binds to host DNA Viral Genes expressedViral Genes expressed

Adenovirus mRNA moves to cytoplasmAdenovirus mRNA moves to cytoplasm 13S mRNA & 12S mRNA have introns13S mRNA & 12S mRNA have introns Intron splicing of mRNA gives several different Intron splicing of mRNA gives several different

proteinsproteins

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Clinical ManifestationsClinical Manifestations

ConjunctivitisConjunctivitis acute folicular conjunctivitisacute folicular conjunctivitis epidemic keratoconjunctivitisepidemic keratoconjunctivitis

Pharyngitis- acute febrilePharyngitis- acute febrilePneumonia- sequalae Pneumonia- sequalae CystitisCystitis Infantile GastroenteritisInfantile Gastroenteritis

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Host DefensesHost Defenses

Neutralizing antibodies -teenagersNeutralizing antibodies -teenagersCytotoxic T lymphocytesCytotoxic T lymphocytesInterferonInterferon

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EpidemiologyEpidemiology

Children Children 6 months-2 years highly susceptible6 months-2 years highly susceptible extends to 5-9 years of ageextends to 5-9 years of age types 2,1,3,5,7types 2,1,3,5,7 type 1 & 2 causes 60% of infectionstype 1 & 2 causes 60% of infections

Military recruitsMilitary recruitsImmunocompromised patientsImmunocompromised patients

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Antigenic typesAntigenic types

MastadenovirusMastadenovirus 47 types of human adenovirus47 types of human adenovirus

Aviadenovirus Aviadenovirus 80 types infect birds80 types infect birds

No common antigen for all adenovirusesNo common antigen for all adenoviruses some cross reaction with hexon proteinsome cross reaction with hexon protein

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Human Adenovirus Types(Mastadenovirus H)

Human Adenovirus Types(Mastadenovirus H)

Subgenus Serotype Subgenus Serotype

A 12,18,31A 12,18,31

B 3,7,11,14,16,21,34,35B 3,7,11,14,16,21,34,35

C 1,2,5,6C 1,2,5,6

D 8-10,13,15,17,20,22-30,D 8-10,13,15,17,20,22-30,

32,33,36-3932,33,36-39

E 4E 4

F 40,41F 40,41

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PathogenesisPathogenesis

Droplet transmissionDroplet transmissionRespiratory or ocular secretionsRespiratory or ocular secretionsPersistent infection in tonsilsPersistent infection in tonsils

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Adenovirus causes epidemics of acute respiratory disease in

military recruits

Adenovirus causes epidemics of acute respiratory disease in

military recruits

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VaccinationVaccination

limited application because adenovirus is limited application because adenovirus is associated with tumorigensis in animalsassociated with tumorigensis in animals

rarely serious complicationrarely serious complicationattenuated vaccine to 4,7,21attenuated vaccine to 4,7,21applied to military recruitsapplied to military recruits

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Adenovirus-Host Cell Interactions

Adenovirus-Host Cell Interactions

Viral latency human- Viral latency human- tonsilstonsils

Abortive infection-Abortive infection-hamsterhamster or monkey cellsor monkey cells

Semi permissive infection- Semi permissive infection- rat cellsrat cells

Productive infection-Productive infection-human cellshuman cells

Malignant transformation- Malignant transformation- rat cell linesrat cell lines

Tumor induction- Tumor induction- hamstershamsters First time for Human virus (Type 12) First time for Human virus (Type 12)

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Adenovirus induced tumour in hamster

Adenovirus induced tumour in hamster

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Adeno Associated Satellite VirusAdeno Associated Satellite Virus

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DiagnosisDiagnosis

Clinical manifestationsClinical manifestationsRise in specific antibody titer between Rise in specific antibody titer between

acute phase and convalescent phaseacute phase and convalescent phaseIsolation of virus by tissue cultureIsolation of virus by tissue culture

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Cytopathic EffectCytopathic Effect

diploid cells, early diploid cells, early cpe-125xcpe-125x

Apoptosis induced Apoptosis induced by E1A proteinsby E1A proteins made from 12S & made from 12S &

13S mRNA13S mRNA

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Cytopathic effect on primary rhesus monkey kidney cells

Cytopathic effect on primary rhesus monkey kidney cells

<<early

late>>

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Adenovirus pneumonitisAdenovirus pneumonitis

bronchial occlusionbronchial occlusion

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Adenovirus inclusionsAdenovirus inclusions

Basophilic nuclear inclusions in lung Basophilic nuclear inclusions in lung alveolialveoli

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Nuclear inclusions of AdenovirusNuclear inclusions of Adenovirus