Herpes Viruses

Herpes Viruses

INTRO
1. Herpesviridae
2. Structure
  1. DNA core
    1. DS DNA
      1. Enters though nuclear pore
  2. Capsid
    1. Capsomeres
    2. Bind microtubules
      1. Transport to nucleas
  3. Tegument
    1. Viral enzymes
  4. Envelope
    1. Glycoprotein spikes
  5. Pro-capsid
    1. VP5 pentons & hexons
Infectious cycle
1. 1.Viral DNA enters nucleus and circularizes
2. 2. IE genes expressed via tegument VP16
3. 3. IE proteins activate E gene
4. 4. Transcription stimulates L genes
  1. structural proteins
5. 5. DNA encapsidation
6. 6. Egress
Success strategies
1. Fast invasion
  1. Inhibit host protein synth
  2. Viral DNA to nucleus
2. Immune evasion
  1. Blocks antigen presentation
  2. Prevents apoptosis
3. Latent persistance
  1. Lymphoma and CNS cells
  2. Chromatin organisation
    1. Express LAT
      1. Promotes heterochromatin formation
    2. VP16 in cytoplasm
      1. Virion transactivatin g protein
      2. Usually suppresses heterochromatin
    3. IE genes repressed
      1. Intermediate early
    4. HCF in cytoplasm
      1. Host cell factor
    5. Regulates gene expression
Main types
1. A.HSV-1
  1. Symptoms
    1. Genital herpes
      1. 2-3d = itching/throbbing
      2. blisters then scabbing
      3. Triggers:
        stress
        immune compromisation
        Complications
        Herpes encephalitis
        Blindness
        Convulsions
        Brain inflammation/oedma
        Neonatal herpes
        gingivostomatitis
        Cold sore like lesions in mouth
        Herpes keratitis
  2. Treatments
    1. Acyclovir
      1. guanine base anologue
        GTP
      2. specific to infected cells
        activated by viral thymidine kinase
    2. Pencyclovir
2. B. Varicellar-zoster virus
  1. Primary infection
    1. Chicken pox
      1. prodrome 1-3d
        headache/malaise
        Fever
      2. Systemic infection
        travels to skin
        pustules
      3. Complications
        Pneumonia
        Congenital
        encephalitis
        Reye's syndrome
      4. Incubation
    2. Vaccine
      1. Varivax
        Attenuated virus
  2. Reccurrent infection
    1. Shingles
      1. symptoms
        blisters encircle trunk
        headaches
        facial paralysis
        Travels down spine
        Dermatomes
3. C.EBV
  1. Infectious mononucleosis
    1. symptoms
      1. fever
      2. sore throat
      3. enlarged lymph nodes/splene
    2. Diagnosis
      1. mononuclear cells
      2. increased lymphoctes
      3. Anti-EBV antibodies
      4. Paul-Bunnel test
  2. Burkitts lymphoma
    1. B cell tumor
      1. EBV DNA present
    2. Treatment
      1. cyclophosphamide
    3. Plasmodium faciparum
      1. Drives Th2 response
        infected B cell prolif.
        benefits EBV
        IL-10
    4. EBV induces
      1. c-myc translocation 8;14
        proto-oncogene proximity to IgH promotor
      2. BIM repression
        BIM = pro-aptotic
  3. Life cycle
    1. 1.saliva
    2. 2. infects naive B cells
      1. Drive B cell prolif. in GC
        LAT genes expressed
    3. 3.terminal differentiation to plasma cells
4. D.CMV
  1. Similar to EBV
  2. Latent in salivary glands and kidney
  3. congenital complications
    1. ie. immunocompromised
5. E.HHV-8
  1. Kaposi sarcoma
    1. common in AIDS
    2. severe due to immune status

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