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  1. 1. Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Adenovirus Infections  Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis (bladder infection), and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Young infants and especially patients with compromised immune systems are more susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), which was first recognized among military recruits during World War II, can be caused by adenovirus infections. Dr.T.V.Rao MD 2
  3. 3. What are Adenoviruses• Adenoviruses are a group of medium sized, nonenvelopedd, double stranded DNA viruses that share a common complement fixing antigen• They infect humans and animals Dr.T.V.Rao MD 3
  4. 4. Adenoviruses Adenoviruses are medium-  sized (90-100 nm), nonenvelopedd icosahedral viruses containing double- stranded DNA. There are at least 52 immunologically distinct types that can cause human infections. Adenoviruses are unusually stable to chemical and physical agents and to adverse pH conditions, thus allowing for prolonged survival outside of the body. Dr.T.V.Rao MD 4
  5. 5. Morphology of Adenovirus• The capsid contains 252 capsomers arranged as icosahedrons with 20 triangular facets and 12 vertices• 240 are called as hexons• 12 are called as pentons. Dr.T.V.Rao MD 5
  6. 6. Isolation of Adenovirus  Adenoviruses were first isolated in human adenoids (tonsils), from which the name is derived. Adenoviruses represent the largest nonenvelopedd viruses, because they are the maximum size able to be transported through the endosome Dr.T.V.Rao MD 6
  7. 7. Classification Contain two genera Mastaadenovirus.  Infects the mammals Aviaadenovirus Infects birds They infect only the homologues species with the exception of oncogenic human adenovirus Type 12, 18,and 31 cause sarcoma when injected into new born hamsters. Doctorraosslideshare Dr.T.V.Rao MD 7
  8. 8. PROPERTIESComposition: • DNA (13%), protein (87%)Genome: • Linear, double stranded DNA, 26 – 45 kbp, protein-bound to termini, infectious Dr.T.V.Rao MD 8
  9. 9. PROPERTIESProteins: • 11 virion proteins • Hexon & penton capsomeres are the major components on the surface of the virus particle • Penton base with toxin-like activity • Fibers – with type-specific antigens; associated with hemagglutinating activity Dr.T.V.Rao MD 9
  10. 10. PROPERTIESReplication: Early Events • Induce the host cell to enter the S phase of the cell cycle  create conditions conducive to viral replication Interaction of Virus attachment penton base with (adsorption) cellular integrins NUCLEUS Virus Uncoating CYTOSOL internalization into endosomes Dr.T.V.Rao MD 10
  11. 11. PROPERTIESVirus Effects on Host Defense Mechanisms • VA RNAs: prevent activation of an interferon-inducible kinase that inactivates eukaryotic initiation factor 2 • E3 region proteins: inhibit cytolysis of infected cells by host responses  E3 gp19-kDa protein: blocks movement of MHC class I antigen to the cell surface  protect from CTL-mediated lysis  Other E3-encoded proteins: block TNF- Dr.T.V.Rao MD 11
  12. 12. PROPERTIESVirus Effects on Cells • Oncogenes: E1A (pRB) and E1B (p53) – animals such as hamsters • Cytopathic for human cell cultures, particularly primary kidney and continuous epithelial cells • CPE: marked rounding, enlargement, and aggregation of affected cells into grape-like clusters without lysis of infected cells Dr.T.V.Rao MD 12
  13. 13. Adenovirus GenomeThe adenovirus genome is linear, non-  segmented double stranded (ds) DNA which is around 30–38 Kbp. This allows the virus to theoretically carry 30 to 40 genes Although this is significantly larger than other viruses in its Baltimore group it is still a very simple virus and is heavily reliant on the host cell for survival and replication. An interesting feature of this viral genome is that it has a terminal 55 kDaprotein associated with each of the 5 ends of the linear ds DNA, these are used as primers in viral replication and ensure that the ends of the virus linear genomeDr.T.V.Raoadequately replicated 13 are MD
  14. 14. Appear as Space Vehicle  Dr.T.V.Rao MD 14
  15. 15. Adenoviruses are prevalent all over the world• Over 50 serotypes are isolated• Most of the recent isolates are from AIDS patients• Infections are common in children and world wide prevalence. Dr.T.V.Rao MD 15
  16. 16. PathogenesisAdenovirus cause  infections inRespiratory tractEye, Urinary bladder, and IntestinesMore than one type of virus may cause clinically different diseases Dr.T.V.Rao MD 16
  17. 17. Immunity • Induce effective and long-lasting immunity against re- infection• Resistance to clinical disease directly related to presence of circulating neutralizing antibodies – persist for life• Type-specific neutralizing antibodies do not always prevent re-infection• Group-specific antibodies not protective and decline with time• Maternal antibodies protective for infants against severe respiratory infections Dr.T.V.Rao MD 17
  18. 18. Clinical Features• Clinical features:  Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Dr.T.V.Rao MD 18
  19. 19. CLINICAL FINDINGSRESPIRATORY DISEASES • Cough, nasal congestion, fever, and sore throat  most common in infants and children; usually involving Group C viruses • Types 3, 7, and 21: pneumonia (10-20%) in childhood • Types 4 and 7 (and occ. Type 3): acute respiratory disease among military recruits; occurs in epidemic form Dr.T.V.Rao MD 19
  20. 20. Adenovirus infections areimportant in Military Medicine Adenoviruses are responsible for 3-5%of acute respiratory infections inchildren and 2% of respiratory illnessesin civilian adults. They are more apt tocause infection among military recruitsand other young people who live ininstitutional environments. Outbreaksamong children are frequently reportedat boarding schools and summer Dr.T.V.Rao MD 20
  21. 21. Adenovirus - PharyngitisMajor cause of infections associated with nonbacterial pharyngitis and tonsillitisCauses febrile common coldTypes 1 – 7 are common types Dr.T.V.Rao MD 21
  22. 22. Adenovirus Common cause of Respiratory infections  Dr.T.V.Rao MD 22
  23. 23. Pneumonia - Adenovirus Adenovirus types 3 and 7 are associated with pneumonia resembles like atypical pneumonia in adults. Type 7 causes serious and even fatal pneumonia in infants and young children Dr.T.V.Rao MD 23
  24. 24. ARD – Acute respiratory disease with AdenovirusOccurs usually in military recruitsSerotypes 4,7,and 21 are agents commonly associated. Dr.T.V.Rao MD 24
  25. 25. Pharyngocongunctival fever• Occurs in civilian population manifest with syndrome of febrile Pharyngitis and conjunctivitis• Serotypes 3, 7, and 14 are associated. Dr.T.V.Rao MD 25
  26. 26. Epidemickeratoconjunctivitis Occurs with serious epidemic Caused by serotypes 8, and less frequently with 19, and 37. Dr.T.V.Rao MD 26
  27. 27. GASTROINTESTINAL DISEASEGASTROINTESTINAL DISEASETypes 40 and 41 • Associated with infantile gastroenteritis • Account for 5-15% of viral gastroenteritis in young children • Abundantly present in diarrheal stools Dr.T.V.Rao MD 27
  28. 28. A severe Adenoviral Infection  Dr.T.V.Rao MD 28
  29. 29. Other manifestations Acute follicular conjunctivitis, types 3,4 and 11 are responsibleAdenoviral and chlamydial conjunctivitis are clinically similarDiarrhoea – not conclusively establishedAcute haemorrhagic cystitis in children and types 11 and 21 are responsibleMesenteric adenitis and intussusceptions in children. Dr.T.V.Rao MD 29
  30. 30. Adenovirus in Immunocompromised • Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), first recognized among military recruits during World War II, can be caused by adenovirus infections during conditions of crowding and stress. Dr.T.V.Rao MD 30
  31. 31. Immunity in Children Most children have  been infected by at least one adenovirus by the time they reach school age. Most adults have acquired immunity to multiple adenovirus types due to infections they had as children. Dr.T.V.Rao MD 31
  32. 32. Diagnosis of Adenoviral Infections Diagnosis: Antigen detection, polymerase chain reaction assay, virus isolation, and serology can be used to identify adenovirus infections. Adenovirus typing is usually accomplished by haemagglutination- inhibition and/or neutralization with type- specific antiserum. Since adenovirus can be excreted for prolonged periods, the presence Dr.T.V.Rao MD 32
  33. 33. LABORATORY DIAGNOSIS• SAMPLES should be collected from affected sites early in the illness• Duration of virus excretion varies among different illnesses  Throat of adults with common cold: 1 – 3 days  Throat, stool, and eye for Pharyngocongunctival fever: 3 – 5 days  Eye for keratoconjunctivitis: 2 weeks  Throat and stool of children with respiratory illnesses: 3 – 6 weeks  Urine, throat and stool of immunocompromised patients: 2 – 12 months Dr.T.V.Rao MD 33
  34. 34. LABORATORY DIAGNOSIS1. Virus isolation in cell culture2. DNA hybridization or restriction endonuclease digestion3. PCR4. Electron microscopy5. ELISA6. Latex agglutination7. Serology Dr.T.V.Rao MD 34
  35. 35. EPIDEMIOLOGY• Usually do not cause outbreaks of disease• Most common serotypes in clinical samples: low numbered respiratory types (1, 2, 3, 5, 7) and the gastroenteritis types (40 and 41)• MOT: direct contact, fecal-oral route, respiratory droplets, or contaminated fomites• Infections with types 1,2,5, and 6 – chiefly during first year of life• Infection with types 3 and 7 – school years• Infection with types 4,8 and 19 – adulthood• Types 34 and 35 – bone marrow and renal transplant recipients Dr.T.V.Rao MD 35
  36. 36. Treatment ? No evidence-based guidelines for or against specific antiviral therapies in this setting are available, and treatment decisions should be individualized; current evidence somewhat favors treatmentSeveral case reports have described success with cidofovir/ribavirin therapy for serious adenoviral disease in immunocompromised patients; however, the number of failed treatments that have not been reported Dr.T.V.Rao MD 36 remains uncertain.
  37. 37. Prevention:  Vaccines were developed for adenovirus serotypes 4 and 7, but were available only for preventing ARD among military recruits, however, vaccine production was stopped in 1999. Strict attention to good infection-control practices, including contact and droplet precautions, is effective for stopping nosocomial outbreaks of adenovirus-associated disease, such as epidemic keratoconjunctivitis. Maintaining adequate levels of chlorination is necessary for preventing swimming pool-associated outbreaks of adenovirus conjunctivitis, and frequent hand hygiene is recommended in group child care settings. Dr.T.V.Rao MD 37
  38. 38. Adenovirus as Vector in Gene therapy Gene therapy using an  Adenovirus vector. A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein. Dr.T.V.Rao MD 38
  39. 39. Created by Dr.T.V.Rao MD for ‘e’ learning resources for Medical professionals in Developing World Email  Dr.T.V.Rao MD 39