Togaviruses & bunyaviruses

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Togaviruses & bunyaviruses

  1. 1. ARBOVIRUSES:TOGAVIRUSES & BUNYAVIRUSES<br />EDWARD-BENGIE L. MAGSOMBOL, MD<br />FPCP, FPCC, DASNC<br />Associate Professor, Department of Microbiology<br />Fatima College of Medicine<br />
  2. 2. I. INTRODUCTION<br />New pathogenic viruses emerging due to human practices<br />500 known arboviruses, 100 pathogenic to humans and 50 to animals<br />includes unrelated viruses that are arthropod-borne but now also includes non-arthropod-borne but morphologically similar viruses (Hantaan)<br />arthropods: mosquitoes, ticks, flies. mites<br />
  3. 3. clinical syndromes: mostly mild, acute, undifferentiated febrile illness<br />complications: rash, hemorrhage, encephalitis, hepatitis or renal failure<br />found in almost all parts of the world including the Arctic<br />Ex. of outbreaks: Rift Valley Fever, Egypt <br /> (1970s)<br /> Yellow fever, West Africa (1986-1991)<br />
  4. 4. II. VIRUS STRUCTURE AND GENETICS<br />Families: Togaviridae, Flaviviridae, Bunyaviridae<br /> Genera: 1. Togaviridae: <br /> 4 members but Alphavirus is the only <br /> arthropod borne<br /> a. Alphavirus : ssRNA (+) stranded<br /> Spherical, 60-70 nm, enveloped<br /> 3 structural CHONs: capsid, <br /> glycosylated E2 and E1<br /> WEE, EEE, VEE<br /> b. Rubivirus : Rubella<br /> c. Pestivirus and Arterivirus (non-pathogenic to humans)<br />
  5. 5. 2. Flaviviridae: ssRNA, (+) stranded, <br /> 40-50 nm, enveloped<br /> 3 structural CHONs: <br /> capsid, <br /> glycosylated CHON<br /> small, membrane associated <br /> non-glycosylated CHON<br /> Ex. dengue, yellow fever, Jap B Encephalitis, <br /> St. Louis Encephalitis, Russian Spring <br /> Summer Encephalitis, Prowasan<br />
  6. 6. 3. Bunyaviridae: Bunyamwera, Phlebovirus, <br /> Nairovirus, Hantavirus<br /><ul><li>80-100 nm, 3-segment genome of (-) stranded RNA
  7. 7. 3 glycosylated CHONs enveloping virions </li></ul> nucleocapsid (M or middle RNA segment)<br /> (S or small RNA segment)<br /> (L or large RNA segment)<br /> no matrix proteins<br /> polymerase, other CHONs<br />
  8. 8. alpha, flavi, and bunya viruses are all sensitive to lipid solvents and heat<br />important survival mechanism: generating genetic diversity<br />escape from immune responses, adaptation to new hosts, alter replication patterns<br /> 1. genetic drift = deletions, mutations and inversions (alpha, flavi, rhabdo)<br /> 2. genetic shift = genome segment reassortment (bunya, orbivirus)<br />recombination= not known for arboviruses<br />
  9. 9. III. DIAGNOSIS<br />due to prior exposure, absolute Ab titers may be misleading<br />virus-specific peptides<br />virus-specific IgM titers helpful only in some cases<br />most accurate method: <br />isolation of virus from serum<br /> culture via: intracerebral inoculation of <br /> suckling mice<br /> continuous cell lines <br /> (mosquito cells)<br />
  10. 10. TOGAVIRUSES<br /><ul><li>Enveloped, positive, single-stranded RNA viruses with icosahedral nucleocapsid
  11. 11. Genome encodes early (non-structural) and late (structural) proteins
  12. 12. Replicate in the cytoplasm and bud at the plasma membrane</li></li></ul><li>TOGAVIRUSES<br />
  13. 13. TOGAVIRUSES<br />
  14. 14. TOGAVIRUSES: Mosquito Vectors<br />Culex<br />Aedes triseriatus<br />Culiseta melanura<br />
  15. 15. TOGAVIRUSES: Alphaviruses<br /><ul><li>Classified as arboviruses (arthropod-borne viruses). To be an arbovirus, the virus must be able to:</li></ul>Infect both vertebrates & invertebrates<br />Initiate sufficient viremia in a vertebrate host for a sufficient time to allow acquisition of the virus by the invertebrate vector<br />Initiate a persistent productive infection of the salivary gland of the invertebrate to provide virus for the infection of other host animals<br />
  16. 16. TOGAVIRUSES: Alphaviruses<br /><ul><li>With broad host range including vertebrates and invertebrates
  17. 17. Diseases spread by animals or with an animal reservoir  zoonotic
  18. 18. Structurally similar to Picornaviruses but larger</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br /><ul><li>Capsid proteins of all Alphaviruses are similar in structure and are antigenically cross-reactive
  19. 19. Individual viruses with different tissue tropisms
  20. 20. Enters the cell by receptor-mediated endocytosis  bind to ribosomes as mRNA</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br /><ul><li>Major differences between Alphaviruses and Flaviviruses are in the organization of their genome and their mechanism of protein synthesis
  21. 21. Entire flavivirus genome translated into a single polyprotein
  22. 22. Replicate in the cytoplasm and bud at the plasma membranes
  23. 23. Flavivirus structural genes are at the 5’ end of the genome  structural proteins synthesized first and with the greatest efficiency</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br /><ul><li>MOT: bite of an arthropod
  24. 24. Humans are usually “dead-end” hosts due to absence of persistent viremia
  25. 25. Female mosquito acquire the viruses by taking a blood meal from a viremic vertebrate host
  26. 26. Most common vector is the mosquito. Birds and mammals are the usual reservoirs.</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br /><ul><li>Diseases occur during the summer months and rainy seasons
  27. 27. Urban outbreaks occur when the reservoirs for the virus are humans or urban animals.
  28. 28. Humans can be reservoirs for dengue, yellow fever, and chikungunya. </li></li></ul><li>TOGAVIRUSES: Alphaviruses<br /><ul><li>Viruses are cytolytic
  29. 29. Viruses establish systemic infection and viremia.
  30. 30. Viruses are good inducers of interferon, accounting for the flu-like symptoms of infection.</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br />Systemic symptoms within 3 to 7 days of infection<br />Initial viremia<br />Replication in cells of monocyte-macrophage system<br />Brain via endothelial cells lining small vessels of the brain or the choroid plexus<br />Secondary viremia<br />Liver, skin, vasculature (depending on tissue tropism of the virus)<br />
  31. 31. TOGAVIRUSES: Alphaviruses<br /><ul><li>Disease characterized as low-grade disease
  32. 32. Flu-like symptoms correlate with systemic infection during the initial viremia
  33. 33. EEE, WEE, and VEE  progress to encephalitis in humans (fever, headache & dec. consciousness 3-10 days after infection)  generally resolve without sequelaebut with possibility of paralysis, mental disability, seizures and death</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br />Chikungunya<br /><ul><li>Swahili for “that which bends up”
  34. 34. Vector: Aedesaegypti
  35. 35. Crippling arthritis with serious disease due to infection with the virus</li></li></ul><li>TOGAVIRUSES: Alphaviruses<br />
  36. 36. TOGAVIRUSES: Alphaviruses<br />Disease Mechanisms of Togaviruses & Flaviviruses<br />
  37. 37. TOGAVIRUSES: Alphaviruses<br />Laboratory Diagnosis:<br />Culture<br /><ul><li>can be grown in both vertebrate and mosquito cell lines but difficult to isolate</li></ul>Cytopathologic studies<br />Immunofluorescence<br />Reverse transcriptase-PCR<br />Serology – hemagglutination inhibition, ELISA, latex agglutination<br /><ul><li>Presence of specific IgM or 4-fold rise in titer between acute and convalescent sera indicate a recent infection</li></li></ul><li>TOGAVIRUSES: Rubella Virus<br /><ul><li>Same structural properties and mode of replication as other togaviruses.
  38. 38. Unlike other togaviruses:</li></ul>It is a respiratory virus<br />It does not cause readily detectable cytopathologic effects<br /><ul><li>Rubella means “little red”
  39. 39. Maternal infection correlated with several other severe congenital defects</li></li></ul><li>TOGAVIRUSES: Rubella Virus<br /><ul><li>Replication of the virus prevents replication of superinfectingpicornaviruses by means of heterologous interference
  40. 40. Infects upper respiratory tract  local LN (+ LAD)  viremia  infection of other tissues
  41. 41. Prodromal period lasts approx. 2 weeks
  42. 42. Viral shedding: prodromal period and for as long as two weeks after onset of rash</li></li></ul><li>TOGAVIRUSES: Rubella Virus<br /><ul><li>Antibody generated after the viremia correlates with appearance of rash  limit viremic spread
  43. 43. Immune complexes most likely cause the rash and arthralgia associated with the infection.
  44. 44. CMI important in resolving the infection
  45. 45. Natural infection produces lifelong protective immunity</li></li></ul><li>TOGAVIRUSES: Rubella Virus<br />Congenital Infection<br /><ul><li>Occurs if mother does not have antibody  virus replicates in the placenta  spread to fetal blood supply & throughout the fetus
  46. 46. Alter normal growth, mitosis, and chromosomal structure of the fetus’s cells
  47. 47. Nature of the disorder determined by:</li></ul>Tissue affected<br />Stage of development disrupted<br />
  48. 48. TOGAVIRUSES: Rubella Virus<br />Congenital Rubella Syndrome<br /><ul><li>Most serious outcome of infection
  49. 49. Fetus at risk until 20th week AOG
  50. 50. Most common manifestations: cataracts, mental retardation, deafness</li></li></ul><li>TOGAVIRUSES: Rubella Virus<br />
  51. 51. TOGAVIRUSES: Rubella Virus<br />Rubella Disease (German Measles)<br /><ul><li>Normally benign in children
  52. 52. I.P. = 14 – 21 days
  53. 53. 3-day maculopapular or macular rash + swollen glands
  54. 54. Infection in adults may be more severe
  55. 55. Arthralgia & arthritis
  56. 56. Thrombocytopenia or post-infectious encephalopathy – rare </li></li></ul><li>TOGAVIRUSES: Rubella Virus<br />
  57. 57. TOGAVIRUSES: Rubella Virus<br />Laboratory Diagnosis<br /><ul><li>Isolation difficult & rarely attempted
  58. 58. Diagnosis confirmed by the presence of anti-rubella-specific IgM
  59. 59. 4-fold increase in specific IgG antibody titer between acute and convalescent sera  recent infection</li></li></ul><li>BUNYAVIRIDAE<br /><ul><li>“Supergroup” of at least 200 enveloped, segmented, negative-strand RNA viruses
  60. 60. Broken down into four genera on the basis of structural and biochemical features
  61. 61. Unlike other negative-strand RNA viruses, they do not have a matrix protein
  62. 62. Replicates in cytoplasm</li></li></ul><li>BUNYAVIRIDAE<br />
  63. 63. BUNYAVIRIDAE<br />
  64. 64. BUNYAVIRIDAE<br /><ul><li>Virus can infect humans and arthropods
  65. 65. Virus in arthropod can be transmitted to its eggs  allow virus to survive during winter
  66. 66. Effects:</li></ul>Neuronal & glial damage + cerebral edema encephalitis<br />Hepatic necrosis (e.g. Rift Valley Fever)<br />Leakage of plasma & erythrocytes through vascular endothelium  hemorrhagic fever<br />
  67. 67. BUNYAVIRIDAE<br /><ul><li>MOT: vectors  mosquitoes, ticks or Phlebotomus flies
  68. 68. Virus transmitted to rodents, birds and larger animals  become reservoirs
  69. 69. Transmission occurs during summer but unlike other arboviruses, many of the Bunyaviridae can survive a winter in the ova of the mosquito</li></li></ul><li>BUNYAVIRIDAE<br /><ul><li>California encephalitis group: Aedestriseriatus & Culiseta
  70. 70. Hantaviruses without arthropod vector  maintained in a rodent species specific for each virus
  71. 71. Humans are infected by close contact with rodents or through the inhalation of aerosolized rodent urine</li></li></ul><li>BUNYAVIRIDAE<br />
  72. 72. BUNYAVIRIDAE<br />Clinical Syndromes:<br /><ul><li>Incubation period: approx. 48 hours
  73. 73. Non-specific febrile flu-like illness
  74. 74. Fever lasts approximately 3 days</li></li></ul><li>BUNYAVIRIDAE<br />Clinical Syndromes:<br />Encephalitis illnesses (e.g. La Crosse)<br /><ul><li>Sudden onset after I.P. of ~ 1 week
  75. 75. Fever, headache, lethargy, vomiting
  76. 76. Seizures in 50% of patients</li></ul>Hemorrhagic fevers (e.g. Rift Valley)<br /><ul><li>Petechialhemorrhages, ecchymoses, epistaxis, hematemesis, melena, gum bleeding </li></li></ul><li>BUNYAVIRIDAE<br />Clinical Syndromes:<br />Hantaan virus<br /><ul><li>Korean hemorrhagic fever
  77. 77. Headache, petechial rash, shock, and renal failure
  78. 78. Rodent-borne</li></ul>Sin Nombre virus<br /><ul><li>Hantavirus pulmonary syndrome
  79. 79. Influenza-like symptoms followed by acute respiratory failure
  80. 80. Endemic in deer mice (Peromyscus)</li></li></ul><li>BUNYAVIRIDAE<br />Laboratory Diagnosis:<br /><ul><li>Serologic tests to confirm diagnosis
  81. 81. ELISA – detect antigen to clinical specimen from patients with intense viremia
  82. 82. RT-PCR – Sin Nombre virus</li></li></ul><li>THANK YOU!<br />

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