Introduction to Adenoviruses

Hugh Fackrell

University of Windsor

Windsor, ON Canada

Fackrel@uwindsor.ca

Adenoviruses Outline

• General Properties of Adenovirus

• Clinical Diseases

• Transmission

• Diagnosis

• Prevention and Control

Baron’s Web Site

Adenovirus Structure

• isocahedral - 70-100 nm

• 252 capsomers
  • 240 hexons
  • 12 fibrillar pentons

• dsDNA linear

• 2 major core proteins
  • 2 minor proteins

Adenovirus Core Proteins

• Protein V- histone like

• Protein VII -bridge to capsid

• Protein mu-??

• Terminal Protein
  • covalently linked to DNA
  • circularizes DNA
  • primer for DNA replication

Model of Adenovirus

Adenovirus virions

Adenovirus replication

Adenovirus mRNA

• Adeno DNA reaches nucleus
  • terminal protein binds to host DNA
  • Viral Genes expressed

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

Clinical Manifestations

• Conjunctivitis
  • acute folicular conjunctivitis
  • epidemic keratoconjunctivitis

• Pharyngitis- acute febrile

• Pneumonia- sequalae

• Cystitis

• Infantile Gastroenteritis

Host Defenses

• Neutralizing antibodies -teenagers

• Cytotoxic T lymphocytes

• Interferon

Epidemiology

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

• Military recruits

• Immunocompromised patients

Antigenic types

• Mastadenovirus
  • 47 types of human adenovirus

• Aviadenovirus
  • 80 types infect birds

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

Human Adenovirus Types(Mastadenovirus H)

Subgenus Serotype

A 12,18,31

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

C 1,2,5,6

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

32,33,36-39

E 4

F 40,41

Pathogenesis

• Droplet transmission

• Respiratory or ocular secretions

• Persistent infection in tonsils

Adenovirus causes epidemics of acute respiratory disease in military recruits

Vaccination

• limited application because adenovirus is associated with tumorigensis in animals

• rarely serious complication

• attenuated vaccine to 4,7,21

• applied to military recruits

Adenovirus-Host Cell Interactions

• Viral latency human- tonsils

• Abortive infection-hamster or monkey cells

• Semi permissive infection- rat cells

• Productive infection-human cells

• Malignant transformation- rat cell lines

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

Adenovirus induced tumour in hamster

Adeno Associated Satellite Virus

Diagnosis

• Clinical manifestations

• Rise in specific antibody titer between acute phase and convalescent phase

• Isolation of virus by tissue culture

Cytopathic Effect

• diploid cells, early cpe-125x

• Apoptosis induced by E1A proteins
  • made from 12S & 13S mRNA

Cytopathic effect on primary rhesus monkey kidney cells

<<early

late>>

Adenovirus pneumonitis

• bronchial occlusion

Adenovirus inclusions

• Basophilic nuclear inclusions in lung alveoli

Nuclear inclusions of Adenovirus