10 Replication of Medium DNA Virus; ssDNA Virus

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wvuong
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186222
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10 Replication of Medium DNA Virus; ssDNA Virus
Updated:
2012-11-30 01:22:47
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virology
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  1. Family
    Adenoviridae
    •“gland”  lymphoid tissue in nasopharynx

    •Icosahedral capsid, 70-90 nm

    •Fiber projections (ligand for attachment)

    •Some adenovirus produce tumors in experimental animals (hamsters)
  2. Genus:  Mastadenovirus
    •“breast”

    •Mammalian species

    •Human adenovirus 1-50

    •Monkeys, horses, cows, pigs, dogs
  3. Genus:  Aviadenovirus
    •“bird”

    •Avian species
  4. Adenovirus
    • •Isolated in 1953 when searching for common
    • cold virus in tonsil & adenoid tissue culture

    • •Latent virus activated, replicates, CPE (cytopathic
    • effect) of cells
  5. Adenovirus
    Infections
    •Upper & lower respiratory infection (URTI, LRTI)

    •Epidemic conjunctivitis

    •Gastroenteritis

    •Acute hemorrhagic cystitis

    •Lytic, chronic, latent, transform cells
  6. URTI:  “Cold”
    •Rhinovirus

    •Coronavirus

    •Adenovirus

    •Parainfluenza virus
  7. URTI:  Pharyngitis
    •Adenovirus

    •Herpes simplex virus (HSV)

    •Enterovirus

    •Epstein-Barr virus (EBV)

    •Less likely:  Influenza virus, Parainfluenza virus, Rhinovirus, Coronavirus
  8. URTI/LRTI:  Croup (Laryngotracheobronchitis)
    •Parainfluenza virus

    • •Respiratory syncytial
    • virus
  9. LRTI:  Bronchiolitis
    •Parainfluenza virus

    • •Respiratory syncytial
    • virus (RSV)
  10. LRTI:  Pneumonia (Lung)
    •Influenza virus

    • •Respiratory syncytial
    • virus (RSV)

    •Parainfluenza virus

    •Adenovirus virus

    •Coronavirus
  11. “Cold”
    Virus Symptoms
    •Fever

    •Cough

    •Headache

    •Sore throat

    •Muscle ache

    •Fatigue

    •± Vomiting, diarrhea
  12. Adenovirus
    Genome:  dsDNA
    • •Linear,
    • 36 kbp

    • •Ends
    • have inverted terminal repeats (ssDNA forms circular structure)

    • •5’
    • end - viral terminal protein (TP, 50 Kd)

    • •Genes
    • found on both DNA strands

    • •Express
    • proteins for: cell activation, DNA synthesis, suppress host immune &
    • inflammatory response, structural capsid
  13. Adenovirus“Early” mRNA
    •From both DNA strands using cell RNA pol II

    • –“right” strand transcription (--->)
    • –“left” strand transcription  (<---)

    •Four early transcription “units”:  E1 – E4

    • –each with separate promoter
    • –E1 enhanced promoter activated by host cell DNA binding proteins

    •mRNAs: 5’cap, 3’polyA tail, post-transcriptionally spliced
  14. Adenovirus:  “Early” Proteins
    • •E1
    • – transformation function, binds cell repressor proteins p105RB & p53

    • •E2
    • – DNA pol, TP, DNA-binding protein (shuts off early
    • promoter)

    • •E3
    • – decreases host MHC proteins & inflammation

    • •E4
    • – decrease host T cell recognition
  15. Host
    Cell Activation 
    • •Adenovirus
    • E1 protein binds cell p105 RB protein

    • •p105 RB no
    • longer functions to down regulate cell transcription

    • •Cell
    • remains active 
  16. Adenovirus
    DNA Replication
    •“Continuous” DNA strand synthesis

    •Replication complex:

    • –viral DNA pol
    • –TP (primer)
    • –DNA-binding proteins (viral & cellular)

    •Type 1 Replication: 

    • –#1 strand copied into dsDNA
    • –#2 strand displaced into ssDNA intermediate

    •Type 2 Replication:  displaced ssDNA copied into dsDNA
  17. Adenovirus:  “Late” mRNA
    • •From one DNA strand
    • – “right” strand transcription (--->)

    •Single promoter:  leader + five mRNAs (L1 – L5) by alternative splicing

    •Translate mainly for structural proteins
  18. Adenovirus:  Splicing of mRNA
    •First observation for splicing of eukaryotic mRNA

    •Hybridize late “hexon” mRNA with single strand viral DNA

    •EM observation that ds RNA:DNA not co-linear, with ssDNA “loops”

    •Deduce that mRNA must be shorter (“exons” – 1,2,3 leader, hexon) and lack certain DNA regions (“introns”- A,B,C)
  19. Adenovirus:  Virus-Associated (VA) RNA
    •By cell RNA pol III

    •Short RNA molecule blocks antiviral action of interferon (stops activation of PKR)

    •Also, E1A protein blocks interferon signal transduction

    •Role in persistent viral infection
  20. Adenoviral
    Vector for Gene Replacement Therapy
    •Eliminate & cut out viral pathogenic gene

    •Insert therapeutic gene,  i.e. insulin gene

    •Infect patient with virus vector to produce insulin in pancreas

    •Complications due to adenovirus infection of various other organs, results in toxicity

    •Vector DNA eventually degraded by cell
  21. Family
    Parvoviridae
    •“small”

    •ssDNA, 5.5 kb

    • icosahedral capsid, 18-26 nm

    •Genus: Parvovirus – mammals and birds

    • •Genus: Dependovirus (adeno-associated
    • viruses) requires  “helper” adenovirus
    • for replication

    •Genus: Densovirus - insects 
  22. Human
    Parvovirus B19
    •Infects mitotically active erythroid precursor cells in bone marrow

    •Erythemia infectiosum (fifth disease) in children – mild flu-like, “slapped cheek” rash

    •Aplastic crisis in hemolytic anemia and in sickle-cell patients

    •Associated with rheumatoid arthritis

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