ADENOVIRUSES; 51 SEROTYPES
RESP. TRACT, GIT, EYE
STRUCTURE
• VIRION: icosahedral, 70-90nm, 25 capsomeres
• Composition; DNA (13%) protein(87%)
• GENOME: ds DNA, linear, 26-45kbp
• Envelope; none
• Replication; nucleus
• Proteins: 11 Ag;
• fibers project from hexon, penton
CLASSIFICATION
• GENERA…..4
• 1 Mastadenovirus; human 51 antigenic types
• Six groups; A-F.
• physical, chemical, biological. genetic basis
• Fibres
• DNA homology; G & C content
• Agglutinate RBC; monkey, rats
REPLICATION
• Replicate only in cells of epitheleal origin
• Early genes…..throughout
• Intermediate genes
• Late genes
VIRAL Attachment
1 via fibre
2 receptor; CAR ( coxsackie virus receptor)
3 internalization in endosomes, then cytosol,
uncoating , nuclear memb. DNA release
EARLY EVENTS
• Host cell enters S phase
• ‘E’ early transcripts from 7 regions of both
strands E1A & E1B involved
• 20 early non-structural proteins made for viral
DNA replication
• LATE EVENTS
• DNA SYNTHESIS
• Structural proteins made; large primary transcript
• 29000 nucleotides; 18 mRNA spliced to
cytoplasm for viral protein synthesis.
VIRAL ASSEMBLY, MATURATION
• Morphogenesis in nucleus: 24 hrs/ 10,000 virion
made/cell
• 3 identical Polypeptides…..
• Hexon capsomere
• Penton…. 5 base polypeptides/ 3 fibre pp
• Capsomeres self assemble as empty capsids in
nucleus
• Naked DNA enters capsids
• Mature particle: stable, infectious, resistant to
nucleases
Viral replication
Virus effect on host defense
• Encode gene products that counter anti-viral
mechanisms
• VA RNA ……counter interferon
• E3 region proteins….prevent cell lysis by host
response
VIRUS EFFECTS ON CELLS
• CYTOPATHIC….. Human cell cultures;
• kidney,
• continuous epithileal cells
• Rounding, enlargement and clustering of cells
• No lysis
• Intranuclear lesions seen
• Crystalline look due to protein
• Viri remain in celll even after death of cell
GENE THERAPY
Gene delivery vehicles for
• cancer therapy; oncolytic therapy…kill cell by
viral rep.
• gene therapy,
• genetic immunization
Limitation:
• CAR : variable expression in various cells
• Failure to integrate in chromosomal DNA
Transforming genes
• Serotypes 12,18, 31 induce tumors in
newborn hamsters
• Al ADV transform cell in culture
• Transforming genes in E1A & EIB
• Alter growth control mechanisms
• Type 12 stops synthesis of class 1 MHC, no
destruction by CTLs
PATHOGENESIS: TYPE 1-7
• Epitheleal cells :
• RT: 5% in children, mild
• GIT
• EYE
• UT
• Limit by regional LN
• Group C persist in adenoids & tonsils
RESPIRATORY; Group C
Children:
• Cough, nasal cong, fever, sore throat;
• Pneumonias(3,7 21); childhood;
• mortality 10-20%
• Military recruits;
• all above in fatigue, stress, crowding( type4,7)
Eye infection
• 1. Children summer camps
• Swimming pool conjunctivitis( type 3.7)
• Recovery in 1-2 weeks
• 2. epidemic keratoconjunctivitus(8,19,37)
• Adults
• contageous,
• resolves in 2 weeks;
• may leave opacities in cornea
GIT
• Serotypes 40 & 41
• Infantile GE
• 5-15% viral GE
• IMMUNOCOMROMISED:5-30%, disseminated
• Transplant; fatal resp disease
• Liver transplant; hepatitis
• Heart , hemopoietic tissue 34-35
• AIDS
Prevention
• Hand wash
• Disinfection
• Chlorination
• Equipment sterilization
• Paper towels
• LIVE VACCINE:1971
• Type 4 &7 in gelatin capsules orally
• Induce Nt AB
immunity
• Effective
• Long lasting due to LN involvement
• Neutralizing AB; life long
• Maternal protection
LAB DIAGOSIS
SWABS: stool, urine , throat, rectal
Diagnosis of current infection: eye, lung, genital tract
1CULTURE: Human cells: embryonic kidney, HeLa, KB
• IF AB used on cells ; anti-hexon AB
• HI & Nt used
2 Nasal epith. Cells stained directly to see Ag
3. PCR; fluids, tissue; conseved seq; hexon, VA1
4. DNA hybridization; restriction endonucleases
5. feces; electron mic, ELIZA; Latex Agg,
Inconclusive unless GE present in pt
SEROLOGY
• Complement –Fixing: AV group Ag
• AB 4 fold rise in sera of acute---convalascent
sera
• Neutralizing anti-body; most sensitivite
• 4* rise
• HI
epidemiology
• Global, all year round
• Resp Tract: low no 1,2,3,5,7 serotypes; 2-5%
• Military; 3,4,7
• Gastro-Entritis; 40,41
• Spread; direct contact, contaminated fomites
• feco-oral, aerosol
• Infant: 1,2,5,6
• School; 3,7
• Adult; 4,8,19
• Eye: hand to eye
• water, swimming pools 3,7
[Micro] adenoviruses
[Micro] adenoviruses
[Micro] adenoviruses

[Micro] adenoviruses

  • 1.
  • 2.
    STRUCTURE • VIRION: icosahedral,70-90nm, 25 capsomeres • Composition; DNA (13%) protein(87%) • GENOME: ds DNA, linear, 26-45kbp • Envelope; none • Replication; nucleus • Proteins: 11 Ag; • fibers project from hexon, penton
  • 6.
    CLASSIFICATION • GENERA…..4 • 1Mastadenovirus; human 51 antigenic types • Six groups; A-F. • physical, chemical, biological. genetic basis • Fibres • DNA homology; G & C content • Agglutinate RBC; monkey, rats
  • 7.
    REPLICATION • Replicate onlyin cells of epitheleal origin • Early genes…..throughout • Intermediate genes • Late genes VIRAL Attachment 1 via fibre 2 receptor; CAR ( coxsackie virus receptor) 3 internalization in endosomes, then cytosol, uncoating , nuclear memb. DNA release
  • 8.
    EARLY EVENTS • Hostcell enters S phase • ‘E’ early transcripts from 7 regions of both strands E1A & E1B involved • 20 early non-structural proteins made for viral DNA replication • LATE EVENTS • DNA SYNTHESIS • Structural proteins made; large primary transcript • 29000 nucleotides; 18 mRNA spliced to cytoplasm for viral protein synthesis.
  • 9.
    VIRAL ASSEMBLY, MATURATION •Morphogenesis in nucleus: 24 hrs/ 10,000 virion made/cell • 3 identical Polypeptides….. • Hexon capsomere • Penton…. 5 base polypeptides/ 3 fibre pp • Capsomeres self assemble as empty capsids in nucleus • Naked DNA enters capsids • Mature particle: stable, infectious, resistant to nucleases
  • 11.
  • 13.
    Virus effect onhost defense • Encode gene products that counter anti-viral mechanisms • VA RNA ……counter interferon • E3 region proteins….prevent cell lysis by host response
  • 14.
    VIRUS EFFECTS ONCELLS • CYTOPATHIC….. Human cell cultures; • kidney, • continuous epithileal cells • Rounding, enlargement and clustering of cells • No lysis • Intranuclear lesions seen • Crystalline look due to protein • Viri remain in celll even after death of cell
  • 15.
    GENE THERAPY Gene deliveryvehicles for • cancer therapy; oncolytic therapy…kill cell by viral rep. • gene therapy, • genetic immunization Limitation: • CAR : variable expression in various cells • Failure to integrate in chromosomal DNA
  • 17.
    Transforming genes • Serotypes12,18, 31 induce tumors in newborn hamsters • Al ADV transform cell in culture • Transforming genes in E1A & EIB • Alter growth control mechanisms • Type 12 stops synthesis of class 1 MHC, no destruction by CTLs
  • 18.
    PATHOGENESIS: TYPE 1-7 •Epitheleal cells : • RT: 5% in children, mild • GIT • EYE • UT • Limit by regional LN • Group C persist in adenoids & tonsils
  • 19.
    RESPIRATORY; Group C Children: •Cough, nasal cong, fever, sore throat; • Pneumonias(3,7 21); childhood; • mortality 10-20% • Military recruits; • all above in fatigue, stress, crowding( type4,7)
  • 21.
    Eye infection • 1.Children summer camps • Swimming pool conjunctivitis( type 3.7) • Recovery in 1-2 weeks • 2. epidemic keratoconjunctivitus(8,19,37) • Adults • contageous, • resolves in 2 weeks; • may leave opacities in cornea
  • 24.
    GIT • Serotypes 40& 41 • Infantile GE • 5-15% viral GE • IMMUNOCOMROMISED:5-30%, disseminated • Transplant; fatal resp disease • Liver transplant; hepatitis • Heart , hemopoietic tissue 34-35 • AIDS
  • 25.
    Prevention • Hand wash •Disinfection • Chlorination • Equipment sterilization • Paper towels • LIVE VACCINE:1971 • Type 4 &7 in gelatin capsules orally • Induce Nt AB
  • 26.
    immunity • Effective • Longlasting due to LN involvement • Neutralizing AB; life long • Maternal protection
  • 27.
    LAB DIAGOSIS SWABS: stool,urine , throat, rectal Diagnosis of current infection: eye, lung, genital tract 1CULTURE: Human cells: embryonic kidney, HeLa, KB • IF AB used on cells ; anti-hexon AB • HI & Nt used 2 Nasal epith. Cells stained directly to see Ag 3. PCR; fluids, tissue; conseved seq; hexon, VA1 4. DNA hybridization; restriction endonucleases 5. feces; electron mic, ELIZA; Latex Agg, Inconclusive unless GE present in pt
  • 28.
    SEROLOGY • Complement –Fixing:AV group Ag • AB 4 fold rise in sera of acute---convalascent sera • Neutralizing anti-body; most sensitivite • 4* rise • HI
  • 29.
    epidemiology • Global, allyear round • Resp Tract: low no 1,2,3,5,7 serotypes; 2-5% • Military; 3,4,7 • Gastro-Entritis; 40,41 • Spread; direct contact, contaminated fomites • feco-oral, aerosol • Infant: 1,2,5,6 • School; 3,7 • Adult; 4,8,19 • Eye: hand to eye • water, swimming pools 3,7