ADENOVIRUS Maria Ellery M. Mendez, MD,  DPASMAP, FPAMS, FPAAAMI  Department of Microbiology  Our Lady of Fatima University
PROPERTIES <ul><li>Virion :  </li></ul><ul><ul><li>Non-enveloped; icosahedral, 70 – 90 nm in diameter, 252 capsomeres (12 ...
PROPERTIES <ul><li>Composition :  </li></ul><ul><ul><li>DNA (13%), protein (87%) </li></ul></ul><ul><li>Genome : </li></ul...
PROPERTIES <ul><li>Proteins :  </li></ul><ul><ul><li>11 virion proteins </li></ul></ul><ul><ul><li>Hexon & penton capsomer...
PROPERTIES <ul><li>Classification: </li></ul><ul><ul><li>Aviadenovirus  (birds) and  Mastadenovirus  (mammals) </li></ul><...
PROPERTIES <ul><li>Replication : Early Events </li></ul><ul><ul><li>Induce the host cell to enter the S phase of the cell ...
PROPERTIES <ul><li>Replication : DNA Replication & Late Events </li></ul><ul><ul><li>Takes place in the nucleus </li></ul>...
PROPERTIES <ul><li>Virus Effects on Host Defense Mechanisms </li></ul><ul><ul><li>VA RNAs:  prevent activation of an inter...
PROPERTIES <ul><li>Virus Effects on Cells </li></ul><ul><ul><li>Oncogenes: E1A (pRB) and E1B (p53) – animals such as hamst...
PROPERTIES <ul><li>Immunity </li></ul><ul><ul><li>Induce effective and long-lasting immunity against re-infection </li></u...
PATHOGENESIS <ul><ul><li>Infect and replicate in epithelial cells of the respiratory tract, eye, GIT, urinary bladder, and...
EPIDEMIOLOGY <ul><li>Usually do not cause outbreaks of disease </li></ul><ul><li>Most common serotypes in clinical samples...
CLINICAL FINDINGS <ul><li>RESPIRATORY DISEASES </li></ul><ul><ul><li>Cough, nasal congestion, fever, and sore throat    m...
CLINICAL FINDINGS <ul><li>EYE INFECTIONS </li></ul><ul><ul><li>Pharyngoconjunctival fever </li></ul></ul><ul><ul><ul><li>O...
CLINICAL FINDINGS EYE INFECTIONS
CLINICAL FINDINGS <ul><li>GASTROINTESTINAL DISEASE </li></ul><ul><li>Types 40 and 41 </li></ul><ul><ul><li>Associated with...
CLINICAL FINDINGS <ul><li>OTHER DISEASES </li></ul><ul><li>Types 11 and 21 </li></ul><ul><ul><li>Acute hemorrhagic cystiti...
LABORATORY DIAGNOSIS <ul><li>SAMPLES should be collected from affected sites early in the illness </li></ul><ul><li>Durati...
LABORATORY DIAGNOSIS <ul><li>Virus isolation in cell culture </li></ul><ul><li>DNA hybridization or restriction endonuclea...
TREATMENT No specific treatment for adenovirus infections
PAPOVAVIRUSES
PROPERTIES <ul><li>Virion :  </li></ul><ul><ul><li>Non-enveloped; icosahedral, 55 nm diameter </li></ul></ul>PAPILLOMA VIRUS
PROPERTIES <ul><li>Composition :  </li></ul><ul><ul><li>DNA (10%), protein (90%) </li></ul></ul><ul><li>Genome: </li></ul>...
PROPERTIES <ul><li>Replication :  </li></ul><ul><ul><li>Nucleus  </li></ul></ul><ul><ul><li>Highly tropic for epithelial c...
PROPERTIES <ul><li>Classification :  </li></ul><ul><ul><li>Based on: </li></ul></ul><ul><ul><ul><li>DNA sequence homology ...
PROPERTIES <ul><li>Outstanding characteristics :  </li></ul><ul><ul><li>Stimulate cell DNA synthesis </li></ul></ul><ul><u...
PATHOGENESIS <ul><li>Infect squamous epithelial cells    induce a characteristic cytoplasmic vacuole ( koilocyte )    ha...
PATHOGENESIS Squamous epithelium of skin (warts) & mucous membrane (genital, oral & conjunctival) (+) epithelial prolifera...
CLINICAL <ul><li>Wart (HPV-1 to HPV-4) </li></ul><ul><ul><li>Benign, self-limited    spontaneous regression </li></ul></u...
CLINICAL <ul><ul><li>Laryngeal papilloma </li></ul></ul><ul><ul><ul><li>Most common benign epithelial tumor of larynx </li...
CLINICAL <ul><li>Anogenital </li></ul><ul><ul><li>Condyloma acuminata </li></ul></ul><ul><ul><li>Squamous epithelium of ex...
CLINICAL Association of HPV with Clinical Lesions HPV TYPE CLINICAL LESION SUSPECTED ONCOGENIC POTENTIAL 1, 4 Plantar wart...
CLINICAL HPV TYPE CLINICAL LESION ONCOGENIC POTENTIAL 7 Hand warts of meat and animal handlers Benign 9,12,14,15,17,19-25,...
CLINICAL COMMON WART
CLINICAL FLAT WARTS
CLINICAL PLANTAR WARTS
CLINICAL MULTIPLE WARTS SUBUNGUAL WART
CLINICAL LABIAL CONDYLOMA
CLINICAL INTERGLUTEAL CONDYLOMA
LABORATORY DIAGNOSIS <ul><li>Histologic examination of tissues </li></ul><ul><ul><li>Hyperkeratosis, koilocytosis </li></u...
PROPERTIES POLYOMA VIRUS <ul><li>Virion: </li></ul><ul><ul><li>Non-enveloped, icosahedral, 45 nm diameter </li></ul></ul><...
PROPERTIES <ul><li>Replication: </li></ul><ul><ul><li>Nucleus </li></ul></ul><ul><li>Classification: </li></ul><ul><ul><li...
PROPERTIES <ul><li>Outstanding characteristics: </li></ul><ul><ul><li>Stimulate cell DNA synthesis </li></ul></ul><ul><ul>...
PROPERTIES <ul><li>Outstanding characteristics: </li></ul><ul><ul><li>Establish persistent and latent infections in kidney...
PATHOGENESIS INHALATION Multiplication in RT Primary viremia KIDNEYS Transient secondary viremia IMMUNOCOMPETENT IMMUNODEF...
CLINICAL <ul><li>BK and JC viruses widely distributed in human populations    (+) specific antibody in 70-80% of adult se...
CLINICAL <ul><li>Primary infection </li></ul><ul><ul><li>Asymptomatic </li></ul></ul><ul><li>Pregnancy </li></ul><ul><ul><...
CLINICAL <ul><li>Progressive multifocal leukoencephalopathy (PML) </li></ul><ul><ul><li>JC virus; subacute demyelinating d...
PARVOVIRUS
PROPERTIES <ul><li>Virion: </li></ul><ul><ul><li>Icosahedral, 18-26 nm diameter, 32 capsomeres; non-enveloped; extremely r...
PROPERTIES <ul><li>Genome: </li></ul><ul><ul><li>Single-stranded DNA, linear, 5.6 kbp, MW 1.5-2.0 million </li></ul></ul><...
PROPERTIES <ul><li>Replication: </li></ul><ul><ul><li>Nucleus </li></ul></ul><ul><ul><li>Dependent on functions of dividin...
PROPERTIES <ul><li>Parvovirus B19 </li></ul><ul><ul><li>Only one serotype </li></ul></ul><ul><ul><li>Replicates in mitotic...
PATHOGENESIS Virus in  URT Local replication Viral replication in erythroid precursor cells in BM Viremia   Rash & arthral...
PATHOGENESIS <ul><li>Principal target: immature cells in erythroid lineage </li></ul><ul><li>Major site of virus replicati...
CLINICAL <ul><li>Erythema Infectiosum (Fifth Disease) </li></ul><ul><ul><li>Most common; I.P. = 1-2 weeks </li></ul></ul><...
CLINICAL
CLINICAL <ul><li>Transient Aplastic Crisis </li></ul><ul><ul><li>Complicate hemolytic anemia – patients with sickle cell d...
CLINICAL <ul><li>Infection in immunodeficient patients </li></ul><ul><ul><li>Cause chronic depression of BM and chronic an...
CLINICAL <ul><li>Infection in pregnancy </li></ul><ul><ul><li>If mother seronegative, pose serious risk to fetus    hydro...
LABORATORY <ul><li>PCR – most sensitive; detected in serum, blood cells, tissue samples, and respiratory secretions </li><...
TREATMENT <ul><li>Fifth disease and transient aplastic crisis – treat symptomatically </li></ul><ul><li>Aplastic crisis – ...
<ul><li>Dependovirus </li></ul><ul><ul><li>Adeno-associated viruses </li></ul></ul><ul><ul><li>Commonly infect humans but ...
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Adenovirus.micro

  1. 1. ADENOVIRUS Maria Ellery M. Mendez, MD, DPASMAP, FPAMS, FPAAAMI Department of Microbiology Our Lady of Fatima University
  2. 2. PROPERTIES <ul><li>Virion : </li></ul><ul><ul><li>Non-enveloped; icosahedral, 70 – 90 nm in diameter, 252 capsomeres (12 vertices or penton bases + 240 hexon capsomeres); fiber projects from each vertex </li></ul></ul>
  3. 3. PROPERTIES <ul><li>Composition : </li></ul><ul><ul><li>DNA (13%), protein (87%) </li></ul></ul><ul><li>Genome : </li></ul><ul><ul><li>Linear, double stranded DNA, 26 – 45 kbp, protein-bound to termini, infectious </li></ul></ul>
  4. 4. PROPERTIES <ul><li>Proteins : </li></ul><ul><ul><li>11 virion proteins </li></ul></ul><ul><ul><li>Hexon & penton capsomeres are the major components on the surface of the virus particle </li></ul></ul><ul><ul><li>Penton base with toxin-like activity </li></ul></ul><ul><ul><li>Fibers – with type-specific antigens; associated with hemagglutinating activity </li></ul></ul>
  5. 5. PROPERTIES <ul><li>Classification: </li></ul><ul><ul><li>Aviadenovirus (birds) and Mastadenovirus (mammals) </li></ul></ul><ul><ul><li>Human adenovirus: six groups (A to F) </li></ul></ul><ul><li>Replication : </li></ul><ul><ul><li>Nucleus; only in cells of epithelial origin </li></ul></ul><ul><ul><li>Attaches to cells via the fiber structures </li></ul></ul><ul><ul><li>Host cell receptor: CAR (coxsackie-adenovirus receptor)  member of immunoglobulin gene superfamily </li></ul></ul>
  6. 6. PROPERTIES <ul><li>Replication : Early Events </li></ul><ul><ul><li>Induce the host cell to enter the S phase of the cell cycle  create conditions conducive to viral replication </li></ul></ul>Virus attachment (adsorption) Interaction of penton base with cellular integrins Virus internalization into endosomes CYTOSOL Uncoating NUCLEUS
  7. 7. PROPERTIES <ul><li>Replication : DNA Replication & Late Events </li></ul><ul><ul><li>Takes place in the nucleus </li></ul></ul><ul><ul><li>Late events begin concomitantly with the onset of viral DNA synthesis </li></ul></ul><ul><ul><li>Host genes continue to be transcribed in the nucleus late in the course of infection </li></ul></ul>
  8. 8. PROPERTIES <ul><li>Virus Effects on Host Defense Mechanisms </li></ul><ul><ul><li>VA RNAs: prevent activation of an interferon-inducible kinase that inactivates eukaryotic initiation factor 2 </li></ul></ul><ul><ul><li>E3 region proteins: inhibit cytolysis of infected cells by host responses </li></ul></ul><ul><ul><ul><li>E3 gp19-kDa protein: blocks movement of MHC class I antigen to the cell surface  protect from CTL-mediated lysis </li></ul></ul></ul><ul><ul><ul><li>Other E3-encoded proteins: block TNF-  </li></ul></ul></ul>
  9. 9. PROPERTIES <ul><li>Virus Effects on Cells </li></ul><ul><ul><li>Oncogenes: E1A (pRB) and E1B (p53) – animals such as hamsters </li></ul></ul><ul><ul><li>Cytopathic for human cell cultures, particularly primary kidney and continuous epithelial cells </li></ul></ul><ul><ul><li>CPE: marked rounding, enlargement, and aggregation of affected cells into grape-like clusters without lysis of infected cells </li></ul></ul>
  10. 10. PROPERTIES <ul><li>Immunity </li></ul><ul><ul><li>Induce effective and long-lasting immunity against re-infection </li></ul></ul><ul><ul><li>Resistance to clinical disease directly related to presence of circulating neutralizing antibodies – persist for life </li></ul></ul><ul><ul><li>Type-specific neutralizing antibodies do not always prevent re-infection </li></ul></ul><ul><ul><li>Group-specific antibodies not protective and decline with time </li></ul></ul><ul><ul><li>Maternal antibodies protective for infants against severe respiratory infections </li></ul></ul>
  11. 11. PATHOGENESIS <ul><ul><li>Infect and replicate in epithelial cells of the respiratory tract, eye, GIT, urinary bladder, and liver </li></ul></ul><ul><ul><li>Usually do not spread beyond the regional LN </li></ul></ul><ul><ul><li>Group C viruses persist as latent infections in adenoids and tonsils  shed in the feces for many months </li></ul></ul><ul><ul><li>Most human adenoviruses replicate in intestinal epithelium after ingestion </li></ul></ul>
  12. 12. EPIDEMIOLOGY <ul><li>Usually do not cause outbreaks of disease </li></ul><ul><li>Most common serotypes in clinical samples: low numbered respiratory types ( 1, 2, 3, 5, 7 ) and the gastroenteritis types ( 40 and 41 ) </li></ul><ul><li>MOT: direct contact, fecal-oral route, respiratory droplets, or contaminated fomites </li></ul><ul><li>Infections with types 1,2,5, and 6 – chiefly during first year of life </li></ul><ul><li>Infection with types 3 and 7 – school years </li></ul><ul><li>Infection with types 4,8 and 19 – adulthood </li></ul><ul><li>Types 34 and 35 – bone marrow and renal transplant recipients </li></ul>
  13. 13. CLINICAL FINDINGS <ul><li>RESPIRATORY DISEASES </li></ul><ul><ul><li>Cough, nasal congestion, fever, and sore throat  most common in infants and children; usually involving Group C viruses </li></ul></ul><ul><ul><li>Types 3, 7, and 21: pneumonia (10-20%) in childhood </li></ul></ul><ul><ul><li>Types 4 and 7 (and occ. Type 3): acute respiratory disease among military recruits; occurs in epidemic form </li></ul></ul>
  14. 14. CLINICAL FINDINGS <ul><li>EYE INFECTIONS </li></ul><ul><ul><li>Pharyngoconjunctival fever </li></ul></ul><ul><ul><ul><li>Occur in outbreaks, such as at children’s summer camps (“ swimming pool conjunctivitis ”); associated with types 3 & 7 </li></ul></ul></ul><ul><ul><li>Epidemic keratoconjunctivitis </li></ul></ul><ul><ul><ul><li>More serious; types 8, 19 and 37 </li></ul></ul></ul><ul><ul><ul><li>Adults; highly contagious </li></ul></ul></ul><ul><ul><ul><li>MOT: fomites (e.g. sinks, hand towels) </li></ul></ul></ul><ul><ul><ul><li>Acute conjunctivitis  keratitis </li></ul></ul></ul>
  15. 15. CLINICAL FINDINGS EYE INFECTIONS
  16. 16. CLINICAL FINDINGS <ul><li>GASTROINTESTINAL DISEASE </li></ul><ul><li>Types 40 and 41 </li></ul><ul><ul><li>Associated with infantile gastroenteritis </li></ul></ul><ul><ul><li>Account for 5-15% of viral gastroenteritis in young children </li></ul></ul><ul><ul><li>Abundantly present in diarrheal stools </li></ul></ul>
  17. 17. CLINICAL FINDINGS <ul><li>OTHER DISEASES </li></ul><ul><li>Types 11 and 21 </li></ul><ul><ul><li>Acute hemorrhagic cystitis in children, especially boys; (+) virus in urine </li></ul></ul><ul><li>Types 1 – 7 </li></ul><ul><ul><li>Respiratory disease progressing to severe pneumonia in transplant patients </li></ul></ul><ul><ul><li>Children with liver transplants – hepatitis </li></ul></ul><ul><ul><li>Children with heart transplants – inc. risk of graft loss </li></ul></ul>
  18. 18. LABORATORY DIAGNOSIS <ul><li>SAMPLES should be collected from affected sites early in the illness </li></ul><ul><li>Duration of virus excretion varies among different illnesses </li></ul><ul><ul><li>Throat of adults with common cold: 1 – 3 days </li></ul></ul><ul><ul><li>Throat, stool, and eye for pharyngoconjunctival fever: 3 – 5 days </li></ul></ul><ul><ul><li>Eye for keratoconjunctivitis: 2 weeks </li></ul></ul><ul><ul><li>Throat and stool of children with respiratory illnesses: 3 – 6 weeks </li></ul></ul><ul><ul><li>Urine, throat and stool of immunocompromised patients: 2 – 12 months </li></ul></ul>
  19. 19. LABORATORY DIAGNOSIS <ul><li>Virus isolation in cell culture </li></ul><ul><li>DNA hybridization or restriction endonuclease digestion </li></ul><ul><li>PCR </li></ul><ul><li>Electron microscopy </li></ul><ul><li>ELISA </li></ul><ul><li>Latex agglutination </li></ul><ul><li>Serology </li></ul>
  20. 20. TREATMENT No specific treatment for adenovirus infections
  21. 21. PAPOVAVIRUSES
  22. 22. PROPERTIES <ul><li>Virion : </li></ul><ul><ul><li>Non-enveloped; icosahedral, 55 nm diameter </li></ul></ul>PAPILLOMA VIRUS
  23. 23. PROPERTIES <ul><li>Composition : </li></ul><ul><ul><li>DNA (10%), protein (90%) </li></ul></ul><ul><li>Genome: </li></ul><ul><ul><li>Double stranded DNA, circular, MW 5 million, 8 kbp </li></ul></ul>
  24. 24. PROPERTIES <ul><li>Replication : </li></ul><ul><ul><li>Nucleus </li></ul></ul><ul><ul><li>Highly tropic for epithelial cells of the skin and mucous membranes </li></ul></ul><ul><ul><li>Viral nucleic acid found in basal stem cells </li></ul></ul><ul><ul><li>Late gene expression (capsid proteins) restricted to uppermost layer of differentiated keratinocytes </li></ul></ul>
  25. 25. PROPERTIES <ul><li>Classification : </li></ul><ul><ul><li>Based on: </li></ul></ul><ul><ul><ul><li>DNA sequence homology </li></ul></ul></ul><ul><ul><ul><li>Tissue tropism – cutaneous or mucosal </li></ul></ul></ul><ul><ul><ul><li>Association with oncogenes </li></ul></ul></ul>
  26. 26. PROPERTIES <ul><li>Outstanding characteristics : </li></ul><ul><ul><li>Stimulate cell DNA synthesis </li></ul></ul><ul><ul><li>Restricted host range and tissue tropism </li></ul></ul><ul><ul><li>Significant cause of human cancer, especially cervical cancer </li></ul></ul><ul><ul><li>Viral oncoproteins (E6 and E7) interact with cellular tumor suppressor proteins (p53 & p105RB) </li></ul></ul><ul><ul><li>Cause lytic infections in permissive cells </li></ul></ul><ul><ul><li>Can immortalize (transform) non-permissive cells </li></ul></ul>
  27. 27. PATHOGENESIS <ul><li>Infect squamous epithelial cells  induce a characteristic cytoplasmic vacuole ( koilocyte )  hallmark of infection </li></ul><ul><li>MOT: </li></ul><ul><ul><li>Direct contact </li></ul></ul><ul><ul><li>Sexual contact </li></ul></ul><ul><ul><li>Passage through infected birth canal </li></ul></ul>
  28. 28. PATHOGENESIS Squamous epithelium of skin (warts) & mucous membrane (genital, oral & conjunctival) (+) epithelial proliferation Hand, foot, throat, eyes, cervix Local multiplication Resolution (latency) Cell transformation
  29. 29. CLINICAL <ul><li>Wart (HPV-1 to HPV-4) </li></ul><ul><ul><li>Benign, self-limited  spontaneous regression </li></ul></ul><ul><ul><li>Infect keratinized surfaces (hand and feet) </li></ul></ul><ul><li>Benign head and neck tumors (HPV 6 and 11) </li></ul><ul><ul><li>Oral papilloma </li></ul></ul><ul><ul><ul><li>Most common benign epithelial tumor of oral cavity </li></ul></ul></ul><ul><ul><ul><li>Any age group; usually solitary </li></ul></ul></ul>
  30. 30. CLINICAL <ul><ul><li>Laryngeal papilloma </li></ul></ul><ul><ul><ul><li>Most common benign epithelial tumor of larynx </li></ul></ul></ul><ul><ul><ul><li>May be life-threatening due to obstruction to airway </li></ul></ul></ul><ul><ul><ul><li>May extend down the trachea & into the bronchi </li></ul></ul></ul>
  31. 31. CLINICAL <ul><li>Anogenital </li></ul><ul><ul><li>Condyloma acuminata </li></ul></ul><ul><ul><li>Squamous epithelium of external genitalia & perianal areas </li></ul></ul><ul><ul><li>Rarely become malignant in healthy people </li></ul></ul><ul><li>Cervical dysplasia and neoplasia </li></ul><ul><ul><li>HPV 16 and 18 </li></ul></ul>
  32. 32. CLINICAL Association of HPV with Clinical Lesions HPV TYPE CLINICAL LESION SUSPECTED ONCOGENIC POTENTIAL 1, 4 Plantar warts Benign 2,4,26,27,29 Common warts Benign 3,10,28,41 Flat warts Rarely malignant 5,8 Epidermodysplasia verruciformis in patients w/ CMI deficiency 30% progress to malignancy 6,11 Anogenital condylomas; laryngeal papillomas; dysplasias and intraepithelial neoplasias Low
  33. 33. CLINICAL HPV TYPE CLINICAL LESION ONCOGENIC POTENTIAL 7 Hand warts of meat and animal handlers Benign 9,12,14,15,17,19-25, 36,46,47 Epidermodysplasia verruciformis Some progress to CA (eg, HPV-17, HPV-20) 13, 32 Oral focal epithelial hyperplasia Possible progression to CA 16,18,30,31,33 35,39,45,51,52 56 High-grade dysplasias & CA of genital mucosa; laryngeal & esophageal CA High correlation with genital & oral CA 34,40,42-44, 53-55, 58, 59, 61,62,64 66-69 Intraepithelial neoplasias (genital, other mucosal sites) Some progress to CA 75,77 Common warts in organ transplant patients 37 Keratoacanthoma Benign
  34. 34. CLINICAL COMMON WART
  35. 35. CLINICAL FLAT WARTS
  36. 36. CLINICAL PLANTAR WARTS
  37. 37. CLINICAL MULTIPLE WARTS SUBUNGUAL WART
  38. 38. CLINICAL LABIAL CONDYLOMA
  39. 39. CLINICAL INTERGLUTEAL CONDYLOMA
  40. 40. LABORATORY DIAGNOSIS <ul><li>Histologic examination of tissues </li></ul><ul><ul><li>Hyperkeratosis, koilocytosis </li></ul></ul><ul><li>Pap smear </li></ul><ul><ul><li>(+) koilocytosis </li></ul></ul><ul><li>DNA molecular probes & PCR – method of choice </li></ul>
  41. 41. PROPERTIES POLYOMA VIRUS <ul><li>Virion: </li></ul><ul><ul><li>Non-enveloped, icosahedral, 45 nm diameter </li></ul></ul><ul><li>Composition: </li></ul><ul><ul><li>DNA 10%, protein (90%) </li></ul></ul><ul><li>Genome: </li></ul><ul><ul><li>Double-stranded, circular, MW 3 million, 5 kbp </li></ul></ul>
  42. 42. PROPERTIES <ul><li>Replication: </li></ul><ul><ul><li>Nucleus </li></ul></ul><ul><li>Classification: </li></ul><ul><ul><li>Humans: BK and JC viruses </li></ul></ul><ul><ul><li>Simian SV40 & murine polyoma – models of tumor-causing viruses </li></ul></ul>
  43. 43. PROPERTIES <ul><li>Outstanding characteristics: </li></ul><ul><ul><li>Stimulate cell DNA synthesis </li></ul></ul><ul><ul><li>Viral oncoproteins (large T and small t) interact with cellular tumor suppressor proteins (large T – p53 & pRB; small t – PP2A or protein phosphatase 2A) </li></ul></ul><ul><ul><li>Can cause human neurologic & renal disease </li></ul></ul><ul><ul><li>May cause human cancer </li></ul></ul>
  44. 44. PROPERTIES <ul><li>Outstanding characteristics: </li></ul><ul><ul><li>Establish persistent and latent infections in kidneys and lungs </li></ul></ul><ul><ul><li>Large T (transformation) antigen: </li></ul></ul><ul><ul><ul><li>Binds to DNA  control early & late gene transcription and viral DNA replication </li></ul></ul></ul><ul><ul><ul><li>Inactivates p53 & p105RB  (+) cell growth </li></ul></ul></ul>
  45. 45. PATHOGENESIS INHALATION Multiplication in RT Primary viremia KIDNEYS Transient secondary viremia IMMUNOCOMPETENT IMMUNODEFICIENT Latent indefinitely in kidney BK virus – urinary tract Hemorrhagic cystitis JC virus – CNS PML
  46. 46. CLINICAL <ul><li>BK and JC viruses widely distributed in human populations  (+) specific antibody in 70-80% of adult sera </li></ul><ul><li>Infection usually occurs in childhood </li></ul><ul><li>Both may persist in the kidneys of healthy individuals but may reactivate when immune response is impaired </li></ul><ul><li>Reactivation: renal transplantation or during pregnancy </li></ul>
  47. 47. CLINICAL <ul><li>Primary infection </li></ul><ul><ul><li>Asymptomatic </li></ul></ul><ul><li>Pregnancy </li></ul><ul><ul><li>Reactivation </li></ul></ul><ul><li>BK virus </li></ul><ul><ul><li>Hemorrhagic cystitis, nephropathy, and severe renal allograft dysfunction </li></ul></ul><ul><ul><li>Cause of polyomavirus-associated nephropathy in renal transplant patients </li></ul></ul>
  48. 48. CLINICAL <ul><li>Progressive multifocal leukoencephalopathy (PML) </li></ul><ul><ul><li>JC virus; subacute demyelinating disease </li></ul></ul><ul><ul><li>Impaired speech, vision, coordination and mentation  paralysis of arms & legs  death </li></ul></ul><ul><ul><li>Normal CSF findings </li></ul></ul>
  49. 49. PARVOVIRUS
  50. 50. PROPERTIES <ul><li>Virion: </li></ul><ul><ul><li>Icosahedral, 18-26 nm diameter, 32 capsomeres; non-enveloped; extremely resistant to inactivation but can be inactivated by formalin,  -propiolactone, and oxidizing agents </li></ul></ul><ul><li>Composition: </li></ul><ul><ul><li>DNA (20%), protein (80%) </li></ul></ul>
  51. 51. PROPERTIES <ul><li>Genome: </li></ul><ul><ul><li>Single-stranded DNA, linear, 5.6 kbp, MW 1.5-2.0 million </li></ul></ul><ul><li>Classification: </li></ul><ul><ul><li>Parvovirinae – vertebrates </li></ul></ul><ul><ul><ul><li>Parvovirus & Erythrovirus – replicate autonomously in rapidly dividing cells </li></ul></ul></ul><ul><ul><ul><li>Dependovirus – depend on a helper virus (adenovirus or herpesvirus) for replication </li></ul></ul></ul><ul><ul><li>Densovirinae – insects </li></ul></ul>
  52. 52. PROPERTIES <ul><li>Replication: </li></ul><ul><ul><li>Nucleus </li></ul></ul><ul><ul><li>Dependent on functions of dividing host cells </li></ul></ul><ul><li>Outstanding Characteristics: </li></ul><ul><ul><li>Smallest DNA virus </li></ul></ul><ul><ul><li>Human pathogen, B19, has tropism for rbc progenitors </li></ul></ul>
  53. 53. PROPERTIES <ul><li>Parvovirus B19 </li></ul><ul><ul><li>Only one serotype </li></ul></ul><ul><ul><li>Replicates in mitotically active cells </li></ul></ul><ul><ul><li>Highly tropic for human erythroid cells </li></ul></ul><ul><ul><li>Cellular receptor: blood group P antigen  expressed on mature rbc, erythroid progenitors, megakaryocytes, endothelia cells, placenta, and fetal liver and heart </li></ul></ul><ul><ul><li>Do not have the ability to stimulate resting cells to initiate DNA synthesis </li></ul></ul>
  54. 54. PATHOGENESIS Virus in URT Local replication Viral replication in erythroid precursor cells in BM Viremia Rash & arthralgia (erythema infectiosum) Normal host (slight drop in hemoglobin) Host with chronic hemolytic anemia Aplastic crisis
  55. 55. PATHOGENESIS <ul><li>Principal target: immature cells in erythroid lineage </li></ul><ul><li>Major site of virus replication: adult marrow and fetal liver </li></ul><ul><li>Induce virus-specific IgG and IgM antibodies </li></ul><ul><li>MOT: </li></ul><ul><ul><li>Respiratory route – major mode </li></ul></ul><ul><ul><li>Parenteral – blood transfusion or infected blood products </li></ul></ul><ul><ul><li>Vertically – mother to fetus </li></ul></ul>
  56. 56. CLINICAL <ul><li>Erythema Infectiosum (Fifth Disease) </li></ul><ul><ul><li>Most common; I.P. = 1-2 weeks </li></ul></ul><ul><ul><li>Children, especially elementary school age </li></ul></ul><ul><ul><li>Rash on cheeks (slapped cheek appearance)  arms and legs (lace-like rash) </li></ul></ul><ul><ul><li>Joint involvement prominent in adults – hands and knees – mimic rheumatoid arthritis </li></ul></ul>
  57. 57. CLINICAL
  58. 58. CLINICAL <ul><li>Transient Aplastic Crisis </li></ul><ul><ul><li>Complicate hemolytic anemia – patients with sickle cell disease, thalassemias, and acquired hemolytic anemias in audlts </li></ul></ul><ul><ul><li>Also occur after BM transplantation </li></ul></ul><ul><ul><li>Abrupt cessation of rbc synthesis in BM </li></ul></ul><ul><ul><li>Symptoms occur during viremic phase of infection </li></ul></ul>
  59. 59. CLINICAL <ul><li>Infection in immunodeficient patients </li></ul><ul><ul><li>Cause chronic depression of BM and chronic anemia in immunocompromised patients </li></ul></ul><ul><ul><li>Disease called pure red cell aplasia </li></ul></ul><ul><ul><li>Severe anemia  dependent on blood transfusions </li></ul></ul><ul><ul><li>Observed in patients with congenital immunodeficiency, malignancies, AIDS and organ transplants </li></ul></ul>
  60. 60. CLINICAL <ul><li>Infection in pregnancy </li></ul><ul><ul><li>If mother seronegative, pose serious risk to fetus  hydrops fetalis (anemia + CHF) </li></ul></ul><ul><ul><li>Fetal death occurs most commonly before the 20 th week of pregnancy </li></ul></ul><ul><ul><li>If mother seropositive  no adverse effect on fetus </li></ul></ul><ul><ul><li>No evidence of physical abnormalities </li></ul></ul>
  61. 61. LABORATORY <ul><li>PCR – most sensitive; detected in serum, blood cells, tissue samples, and respiratory secretions </li></ul><ul><li>Serology </li></ul><ul><ul><li>B19 IgM antibody – recent infection; present 2-3 months after infection </li></ul></ul><ul><ul><li>B19 IgG antibody – chronic infection; persists for years </li></ul></ul>
  62. 62. TREATMENT <ul><li>Fifth disease and transient aplastic crisis – treat symptomatically </li></ul><ul><li>Aplastic crisis – require transfusion therapy </li></ul><ul><li>Commercial Ig preparations – can cure or ameliorate persistent B19 infections in immunocompromised patients and those with anemia </li></ul>
  63. 63. <ul><li>Dependovirus </li></ul><ul><ul><li>Adeno-associated viruses </li></ul></ul><ul><ul><li>Commonly infect humans but replicate only in association with a second “helper” virus, usually Adenovirus </li></ul></ul><ul><ul><li>Neither cause illness or modify infection by their helper viruses </li></ul></ul><ul><ul><li>Can integrate into the host chromosome  good candidate for use in gene replacement therapy </li></ul></ul>
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