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The Adenoviruses

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The Adenoviruses Powered By Docstoc
					The Adenoviruses




 Dr. Mohammad Al-Sweify
       General characters

   first isolated in 1953 in a human adenoid cell culture.
   ~ 47 serotypes are human pathogens.
   RTI, conjunctivitis (pinkeye), hemorrhagic cystitis,
    and gastroenteritis.
   Adenovirus is being used to as vector to deliver DNA
    for gene replacement therapy (e.g., cystic fibrosis).
       Structure and replication
   Adenoviruses are double-stranded DNA,
    nonenveloped, icosadeltahedrons, 70-90 nm.
   12 pentons, at each of the vertices, each
    with a base and a fiber.
   The fiber contains the viral attachment
    proteins and act as a hemagglutinin.
   The pentons and fibers also carry type-
    specific antigens (47 serotypes).
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         Structure & Replication..cont..




   Adenovirus encodes DNA polymerase.
   Also, a proteins that suppress host immune
    and inflammatory responses.
   One replication cycle takes 32-36 h 10,000
    viruses.
   Virus attachment:
       ~100,000 fiber receptors on each cell.
       Same receptor used by many Coxsackie B viruses.
       Some adenoviruses use MHC I mol. as a receptor.
         Structure & Replication..cont..




   Internalization: by receptor-mediated endocytosis in
    vesicle.
   It lyses the endosomal vesicle
   capsid delivers the DNA genome to the nucleus.
   The penton and fiber proteins of the capsid are toxic
    to the cell and can inhibit cellular macromolecular
    synthesis.
   Adenovirus causes lytic (muco-epithelium), persistent
    and latent infections (lymphoid, adenoid, tonsils,
    Peyer’s patche)  reactivation in ISP.
         Pathogenesis


   The virus infects oropharynx, respiratory and enteric
    organs epithelium, depending on fiber proteins that
    determine the target cell specificity.
   Toxic penton base protein inhibits cellular mRNA
    transport and protein synthesis cell rounding, and
    tissue damage.
   CPE of adenovirus: a dense, central intranuclear
    inclusion consisting of viral DNA and protein.
   Mononuclear cell infiltration and epithelial cell
    necrosis.
         Immunity to adenoviruses

   Antibody is important for:
      resolving lytic infections

      protects from reinfection with the same serotype.

   Cell-mediated immunity is important in limiting virus growth.

   Mechanisms to evade host defenses (to persist in the host):
     small virus-associated RNAs (VA RNA) prevent activation of
      IFN-induced inhibition of viral protein synthesis.
     Viral E3 and E1A proteins block apoptosis induced by
      cellular responses to the virus or by T cell or cytokine (e.g.,
      TNF-α) actions.
     Some strains can inhibit Tc-cell action by preventing proper
      expression of MHC I molecules no antigen presentation.
            Epidemiology

   Adenov. resist drying, detergents, GIT juices, and
    even mild chlorine treatment
   Can be spread by aerosol, fecal-oral route, close
    contact, by fomites (including towels and medical
    instruments), and in swimming pools.
   Fingers spread virus to eyes.
   Adenov. may be shed intermittently and over long
    periods from pharynx and in feces.
   Most infections are asymptomatic  spread in the
    community.
         RT clinical illnesses by adenoviruses:


1.   Pharyngitis alone occurs in young children<3 y.
        It may mimic streptococcal infection.
        Affected patients have mild, flulike symptoms (including
         nasal congestion, cough, coryza, malaise, fever, chills,
         myalgia, and headache) that may last 3-5 d.


2.   Pharyngo-conjunctival fever in children and adults.
RT clinical illnesses by adenoviruses..continued..




3.   ACUTE RESPIRATORY DISEASE: a syndrome consisting of
     fever, cough, pharyngitis, and cervical adenitis.
       Usually caused by adenovirus serotypes 4 and 7.
       high incidence of infection of military recruits.

4.   OTHER RESPIRATORY TRACT DISEASES
      Adenoviruses cause cold-like symptoms, laryngitis, croup,
       and bronchiolitis.
      They can also cause a pertussis-like illness in children and
       adults that consists of a prolonged clinical course and true
       viral pneumonia.
Lab diagnosis:
   Culture from clinical specimen on
    primary human embryonic kidney cells,
    or HeLa cells  2-20 days lytic infection
    with characteristic nuclear inclusions
   Immunoassays: FA and ELISA
   PCR and DNA probe analysis
   Serologic test: not used.