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HERPESVIRIDAE herpein:  Greek:  to creep
Herpes simplex 1 and 2 (To “The sound of silence” Simon and Garfunkle) Hello, herpes, our old friend Will be with us to the end. ‘ Cause the virus softly creeping Left its genes while we were sleeping Not integrated into our genome, It will roam that episome. The DNA of herpes.
Herpesviruses ,[object Object],[object Object],[object Object],[object Object],[object Object],The case of the elephant herpesviruses T.rex at exam time
The case of the elephant herpesviruses  (Richman et al. 1999. Science 283:1171) Asian elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in African elephants African elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in Asian elephants
The elephant herpesvirus   Richman et al. 1999. Science 283:1171
Viruses with ds DNA genomes Poxviridae African swine fever virus Herpesviridae Adenoviridae Papovaviridae bovine  herpesvirus-1,2 porcine  cytomegalovirus equine  herpesviruses -1,4 malignant catarrhal fever virus
CLASSIFICATION
CLASSIFICATION
GENERAL CHARACTERISTICS
Herpesvirus Family Tree (Genetic) CLASSIFICATION GAMMAHERPESVIRUSES EHV2 HVS HHV8 EBV HSV1 HSV2 EHV1 PRV VZV ALPHAHERPESVIRUSES BETAHERPESVIRUSES HHV7 HHV6 HCMV
Structure nucleocapsid envelope tegument glycoproteins (gB, gC…gL)
GENERAL CHARACTERISTICS
GENERAL CHARACTERISTICS
BIOLOGICAL PROPERTIES
REPLICATION The genome structure of herpesviruses:  (A) Alphaherpesvirus genomes comprise two regions designated long (L) and short (S).  Terminal repeat (TR) and internal repeat (IR) sequences may bracket unique sequences (U L , U S ) of both L and S or only S.  Repeat sequences are shown as boxes and are encoded as indicated by the direction of the arrows.  Repeat sequences allow the DNA they bracket to invert relative to the rest of the genome such that where both U L  and U S  are bracketed by repeat sequences, four isomers are made and packaged in equimolar amounts into virions.  Where only S is bracketed by repeat sequences, two equimolar isomers are made.  (B) The genome of equine herpesvirus 2, a betaherpesvirus, contains terminal direct repeat structures.  (C) The genome of bovine herpesvirus 4, a gammaherpesvirus, contains multiple direct terminal repeat sequences (small boxes) in a nonequal, variable number of copies.
Replicative cycle inclusion body cell-cell spread
REPLICATION Diagram representing transcription, translation, and DNA replication of a typical herpesvirus.  Transcription and posttranscriptional processing occur in the nucleus, translation in the cytoplasm, and some of the    and    proteins are involved in further transcription and some    proteins in DNA replication.
Productive and latent infections
Viral DNA Latency and Reactivation LAT IE genes (regulatory) E genes (enzymes) L genes (structural) stress immunosuppression corticosteroids cAMP reactivation
Herpesviruses That Cause Diseases in Domestic Animals
DISEASES CAUSED BY HERPESVIRUSES
Bovine herpesviruses
BHV-1(IBR virus) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Infection in the animal reactivation from latency replication in epithelial cells (rhinotracheitis) Infection of susceptible animal systemic cell-associated spread infection of the fetus -> abortion encephalitis replication in epithelial cells establishment of latency (infection for the first time)
Primary lesion
Clinical and immunological parameters
Complications of BHV-1 infection ,[object Object],[object Object],[object Object],[object Object],[object Object]
Factors contributing to shipping fever ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Diagnosis of BHV ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vaccination against BHV-1 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Intranasal vs intramuscular vaccines Route of Inoculation Advantages Disadvantages Intra nasal Stimulates mucosal and systemic immunity. Stimulates interferon. Less affected by maternal antibody. Immunity not as long-lasting as IM. Serum antibody titres lower. Difficult to administer. Intra muscular Longer lasting, higher levels of immunity. Susceptible to maternal antibody.
Considerations for vaccination ,[object Object],[object Object]
Vaccines for eradication gB gB gB gB gene for gE deleted gE gB infected vaccinated ELISA for antibodies infected vaccinated gD subunits gE gD gD gD
DISEASES CAUSED BY HERPESVIRUSES
PRV - Aborted Fetuses DISEASES CAUSED BY HERPESVIRUSES
Neonatal:  Infection DISEASES CAUSED BY HERPESVIRUSES
CNS Signs DISEASES CAUSED BY HERPESVIRUSES
PRV Encephalitis - in situ DISEASES CAUSED BY HERPESVIRUSES
PRV - Pneumonia DISEASES CAUSED BY HERPESVIRUSES
PRV - Infected tonsils - in situ DISEASES CAUSED BY HERPESVIRUSES
DISEASES CAUSED BY HERPESVIRUSES
DISEASES CAUSED BY HERPESVIRUSES
 
Pruritis in Mice DISEASES CAUSED BY HERPESVIRUSES
DISEASES CAUSED BY HERPESVIRUSES
DISEASES CAUSED BY HERPESVIRUSES
Equine herpesviruses ,[object Object]
EHV-1 and EHV-4 ,[object Object],[object Object],[object Object],[object Object],[object Object]
EHV-1 and EHV-4 (respiratory disease) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Pathogenesis of EHV-1 abortions: bronchioles EHV infects endothelial cells and leukocytes cell-associated viremia IL2 induces Adhesion molecules inflammation Thrombotic occlusion vasculitis Virus infects fetus Endometrial vessel
[object Object],[object Object],[object Object],[object Object],[object Object],Key stages in pathogenesis (Allen et al., 1998)
efferent lymphatic EHV-1 epithelial invasion and generation of viremia   Infected endothelial  cells in epithelial lamina propria Infected T lymphocytes  in drainage lymph nodes Viremia Infection of  epithelium and  lamina propria (Kydd et al., 1994)
Viremia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Circulatory immune responses: summary ,[object Object],[object Object],[object Object],[object Object]
EHV-1 abortions ,[object Object],[object Object],[object Object]
Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis
Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis  extensive infarction:  virus negative fetus
Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis  extensive infarction:  virus negative fetus limited infarction:  virus positive fetus
Myeloencephalopathy by EHV-1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Prevention of EHV-1 disease ,[object Object],[object Object],[object Object],[object Object],[object Object]
Other herpesviruses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
DISEASES CAUSED BY HERPESVIRUSES
canine herpesvirus ,[object Object],[object Object],[object Object],[object Object]
feline herpesvirus ,[object Object],[object Object],[object Object],[object Object],[object Object]
DISEASES CAUSED BY HERPESVIRUSES
DISEASES CAUSED BY HERPESVIRUSES
Marek’s disease ,[object Object],[object Object],[object Object],[object Object]
DISEASES CAUSED BY HERPESVIRUSES
beta herpesvirus - porcine cytomegalovirus ,[object Object],[object Object],[object Object],[object Object],[object Object]
DISEASES CAUSED BY HERPESVIRUSES
malignant catarrhal fever (gamma herpesvirus) other ruminants ? other species malignant catarrhal fever
clinical signs in susceptible species ,[object Object],[object Object],[object Object],[object Object],[object Object]
acute MCF
IMMUNE RESPONSES TO HERPESVIRUSES
IMMUNE RESPONSES TO HERPESVIRUSES
IMMUNE RESPONSES TO HERPESVIRUSES
IMMUNE RESPONSES TO HERPESVIRUSES 1 st Generation  - Conventional killed - Modified-live - e.g. PR- Vac, Pseudo  vax 2 nd Generation  - Gene-deleted, i.e. virulence genes - e.g. Omni Vac-1 3 rd Generation - Gene-deleted, i.e. differential marker - e.g. PRV-marker,  Tolvid  Omnivac II 4 th Generation  - Multiple marker genes - e.g. PRV-Gold ?? 
IMMUNE RESPONSES TO HERPESVIRUSES

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Herpes v

  • 1. HERPESVIRIDAE herpein: Greek: to creep
  • 2. Herpes simplex 1 and 2 (To “The sound of silence” Simon and Garfunkle) Hello, herpes, our old friend Will be with us to the end. ‘ Cause the virus softly creeping Left its genes while we were sleeping Not integrated into our genome, It will roam that episome. The DNA of herpes.
  • 3.
  • 4. The case of the elephant herpesviruses (Richman et al. 1999. Science 283:1171) Asian elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in African elephants African elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in Asian elephants
  • 5. The elephant herpesvirus Richman et al. 1999. Science 283:1171
  • 6. Viruses with ds DNA genomes Poxviridae African swine fever virus Herpesviridae Adenoviridae Papovaviridae bovine herpesvirus-1,2 porcine cytomegalovirus equine herpesviruses -1,4 malignant catarrhal fever virus
  • 10. Herpesvirus Family Tree (Genetic) CLASSIFICATION GAMMAHERPESVIRUSES EHV2 HVS HHV8 EBV HSV1 HSV2 EHV1 PRV VZV ALPHAHERPESVIRUSES BETAHERPESVIRUSES HHV7 HHV6 HCMV
  • 11. Structure nucleocapsid envelope tegument glycoproteins (gB, gC…gL)
  • 15. REPLICATION The genome structure of herpesviruses: (A) Alphaherpesvirus genomes comprise two regions designated long (L) and short (S). Terminal repeat (TR) and internal repeat (IR) sequences may bracket unique sequences (U L , U S ) of both L and S or only S. Repeat sequences are shown as boxes and are encoded as indicated by the direction of the arrows. Repeat sequences allow the DNA they bracket to invert relative to the rest of the genome such that where both U L and U S are bracketed by repeat sequences, four isomers are made and packaged in equimolar amounts into virions. Where only S is bracketed by repeat sequences, two equimolar isomers are made. (B) The genome of equine herpesvirus 2, a betaherpesvirus, contains terminal direct repeat structures. (C) The genome of bovine herpesvirus 4, a gammaherpesvirus, contains multiple direct terminal repeat sequences (small boxes) in a nonequal, variable number of copies.
  • 16. Replicative cycle inclusion body cell-cell spread
  • 17. REPLICATION Diagram representing transcription, translation, and DNA replication of a typical herpesvirus. Transcription and posttranscriptional processing occur in the nucleus, translation in the cytoplasm, and some of the  and  proteins are involved in further transcription and some  proteins in DNA replication.
  • 18. Productive and latent infections
  • 19. Viral DNA Latency and Reactivation LAT IE genes (regulatory) E genes (enzymes) L genes (structural) stress immunosuppression corticosteroids cAMP reactivation
  • 20. Herpesviruses That Cause Diseases in Domestic Animals
  • 21. DISEASES CAUSED BY HERPESVIRUSES
  • 23.
  • 24. Infection in the animal reactivation from latency replication in epithelial cells (rhinotracheitis) Infection of susceptible animal systemic cell-associated spread infection of the fetus -> abortion encephalitis replication in epithelial cells establishment of latency (infection for the first time)
  • 27.
  • 28.
  • 29.
  • 30.
  • 31. Intranasal vs intramuscular vaccines Route of Inoculation Advantages Disadvantages Intra nasal Stimulates mucosal and systemic immunity. Stimulates interferon. Less affected by maternal antibody. Immunity not as long-lasting as IM. Serum antibody titres lower. Difficult to administer. Intra muscular Longer lasting, higher levels of immunity. Susceptible to maternal antibody.
  • 32.
  • 33. Vaccines for eradication gB gB gB gB gene for gE deleted gE gB infected vaccinated ELISA for antibodies infected vaccinated gD subunits gE gD gD gD
  • 34. DISEASES CAUSED BY HERPESVIRUSES
  • 35. PRV - Aborted Fetuses DISEASES CAUSED BY HERPESVIRUSES
  • 36. Neonatal: Infection DISEASES CAUSED BY HERPESVIRUSES
  • 37. CNS Signs DISEASES CAUSED BY HERPESVIRUSES
  • 38. PRV Encephalitis - in situ DISEASES CAUSED BY HERPESVIRUSES
  • 39. PRV - Pneumonia DISEASES CAUSED BY HERPESVIRUSES
  • 40. PRV - Infected tonsils - in situ DISEASES CAUSED BY HERPESVIRUSES
  • 41. DISEASES CAUSED BY HERPESVIRUSES
  • 42. DISEASES CAUSED BY HERPESVIRUSES
  • 43.  
  • 44. Pruritis in Mice DISEASES CAUSED BY HERPESVIRUSES
  • 45. DISEASES CAUSED BY HERPESVIRUSES
  • 46. DISEASES CAUSED BY HERPESVIRUSES
  • 47.
  • 48.
  • 49.
  • 50. Pathogenesis of EHV-1 abortions: bronchioles EHV infects endothelial cells and leukocytes cell-associated viremia IL2 induces Adhesion molecules inflammation Thrombotic occlusion vasculitis Virus infects fetus Endometrial vessel
  • 51.
  • 52. efferent lymphatic EHV-1 epithelial invasion and generation of viremia Infected endothelial cells in epithelial lamina propria Infected T lymphocytes in drainage lymph nodes Viremia Infection of epithelium and lamina propria (Kydd et al., 1994)
  • 53.
  • 54.
  • 55.
  • 56. Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis
  • 57. Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis extensive infarction: virus negative fetus
  • 58. Pathogenesis of abortion viremia endometrial endothelial cell infection endometrial vasculitis and thrombosis extensive infarction: virus negative fetus limited infarction: virus positive fetus
  • 59.
  • 60.
  • 61.
  • 62. DISEASES CAUSED BY HERPESVIRUSES
  • 63.
  • 64.
  • 65. DISEASES CAUSED BY HERPESVIRUSES
  • 66. DISEASES CAUSED BY HERPESVIRUSES
  • 67.
  • 68. DISEASES CAUSED BY HERPESVIRUSES
  • 69.
  • 70. DISEASES CAUSED BY HERPESVIRUSES
  • 71. malignant catarrhal fever (gamma herpesvirus) other ruminants ? other species malignant catarrhal fever
  • 72.
  • 74. IMMUNE RESPONSES TO HERPESVIRUSES
  • 75. IMMUNE RESPONSES TO HERPESVIRUSES
  • 76. IMMUNE RESPONSES TO HERPESVIRUSES
  • 77. IMMUNE RESPONSES TO HERPESVIRUSES 1 st Generation  - Conventional killed - Modified-live - e.g. PR- Vac, Pseudo vax 2 nd Generation  - Gene-deleted, i.e. virulence genes - e.g. Omni Vac-1 3 rd Generation - Gene-deleted, i.e. differential marker - e.g. PRV-marker, Tolvid Omnivac II 4 th Generation  - Multiple marker genes - e.g. PRV-Gold ?? 
  • 78. IMMUNE RESPONSES TO HERPESVIRUSES