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 genesVIRAL Attachment1 via fibre2 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 virionmade/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 tract1CULTURE: Human cells: embryonic kidney, HeLa, KB• IF AB used on cells ; anti-hexon AB• HI & Nt used2 Nasal epith. Cells stained directly to see Ag3. PCR; fluids, tissue; conseved seq; hexon, VA14. DNA hybridization; restriction endonucleases5. 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---convalascentsera

• 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