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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). ÏÚÇ Á ÎÊã Ç áÞÑÇ ä.mp3 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.
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