Herpes v
Upcoming SlideShare
Loading in...5
×
 

Herpes v

on

  • 1,008 views

prezentare power point herpes bla bla bla :)

prezentare power point herpes bla bla bla :)

Statistics

Views

Total Views
1,008
Views on SlideShare
1,008
Embed Views
0

Actions

Likes
0
Downloads
25
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Herpes v Herpes v Presentation Transcript

    • 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 Ubiquitous, all vertebrate species ds DNA, approximately 100 genes Co-evolved with their hosts, well adjusted Enveloped Latent infections 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) Infectious bovine rhinotracheitis Disseminated fatal disease of newborns Abortions Genital lesions Encephalitis
    • 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 abortions encephalitis fatal disease in newborn calves Shipping fever (P. hemolytica, P. multocida) Bronchopneumonia -> fibrinous pleuropneumonia
    • Factors contributing to shipping fever Environmental Crowding animals from different sources Stress Host-virus Paralysis of mucociliary escalator Release of iron and nutrients Increased colonization immunosuppression
    • Diagnosis of BHV Virus isolation Immunofluorescence Immunohistochemistry PCR Serology Virus neutralization ELISA
    • Vaccination against BHV-1 Modified-live (attenuated) Intra nasal Intra muscular Inactivated Intra muscular
    • 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 Economics New born calves
    • 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 9 types, 1,3 and 4 are of veterinary importance
    • EHV-1 and EHV-4 Immunologically related Respiratory disease EHV-1causes abortions, neurological disease Immunity short lived Reinfection or reactivation
    • EHV-1 and EHV-4 (respiratory disease) Incubation period (2-10 days) Primary infection in young horses Biphasic fever Nasal discharge, cough Uncomplicated cases -> complete recovery 1-2 weeks
    • 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
    • Respiratory epithelium Lamina propria Drainage lymph nodes Circulation Dissemination of infection 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 central to pathogenesis strictly cell associated EHV-1 infects mainly CD5+/CD8+ T lymphocytes (Scott et al., 1983; Slater et al., 1994; Meulen et al., 2000) associated with neutropaenia and lymphopaenia termination of viraemia requires generation of class I restricted, CD8+ cytotoxic T lymphocytes (CTL) (Allen et al., 1995; O’Neill et al., 1999) viremic lymphocytes express virus antigens briefly and are only transient targets for CTL after this virus persists in lymphocytes in a latent form
    • Circulatory immune responses: summary Strong humoral response to infection with transient CF and longer lived VN antibody responses (Thompson et al. 1976) Protection from reinfection is short lived (Allen and Bryans 1986) No correlation between circulating antibody levels and protection from re-infection (Hannant et al. 1993; Mumford et al. 1994) MHC I restricted CD8+ CTL responses are generated in response to infection (Allen et al. 1995)
    • EHV-1 abortions Late in gestation (7th to 11th month) Few weeks to several months after respiratory outbreak Abortion storms
    • 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 Often but not always associated with respiratory disease Often several horses Sudden onset rapid progression, early stabilization Ataxia, paresis, urinary incontinence, cystitis Little evidence of viral replication in neural tissues (immune mediated?) Vasculitis, thrombosis, hemorrhages (See Wilson, Vet Clin N. Am - equine pract. 1997 13:53)
    • Prevention of EHV-1 disease Management Vaccines Short-lived immunity (mares - 5,7,9 months of gestation Reduce severity but do not prevent Exacerbate myeloencephalitis??
    • Other herpesviruses alpha herpesviruses Canine herpesvirus Feline herpesvirus Marek’s disease beta herpesviruses porcine cytomegalovirus gamma herpesviruses malignant catarrhal fever
    • DISEASES CAUSED BY HERPESVIRUSES
    • canine herpesvirus wide-spread, usually asymptomatic generalized fatal disease in puppies (fading puppy syndrome) hypothermia no vaccine
    • feline herpesvirus feline rhinotracheitis wide spread in catteries respiratory infections abortions - no direct viral involvement vaccines
    • DISEASES CAUSED BY HERPESVIRUSES
    • DISEASES CAUSED BY HERPESVIRUSES
    • Marek’s disease lymphoproliferative, neurological disease of young chickens unilateral paralysis, ataxia due to infiltration of spinal nerves involvement of iris, skin stable in feather follicle dander
    • DISEASES CAUSED BY HERPESVIRUSES
    • beta herpesvirus - porcine cytomegalovirus asymptomatic if endemic in herds in susceptible herds inclusion body rhinitis fetal death runting, poor growth in young piglets
    • DISEASES CAUSED BY HERPESVIRUSES
    • malignant catarrhal fever (gamma herpesvirus) other ruminants ? other species malignant catarrhal fever
    • clinical signs in susceptible species peracute high fever, diarrhoea, death in 1-3 days acute fever, depression, enlarged lymph nodes, serous nasal discharge, erosive lesions, corneal opacity, high mortality chronic form
    • 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