What is new on HHV 6,7,8 infections?, Henry J.C. de Vries

download What is new on HHV 6,7,8 infections?, Henry J.C. de Vries

If you can't read please download the document

Embed Size (px)

description

 

Transcript of What is new on HHV 6,7,8 infections?, Henry J.C. de Vries

  • 1. Henry J.C. de Vries Dermatology Academic Medical Centre University of AmsterdamThe Netherlands

2.

  • Until 1986, 5 herpes viruses
  • new human herpes viruses (HHV)
  • HHV-6 and -7
    • both members of theRoseolovirusgenus of the -herpesviruses.
    • T-lymphotropic but can infect other cell types
    • primary infections are associated withroseola infantum(a.k.a.exanthem subitumor 6th disease)

3.

  • HHV lifetime infection
  • ubiquitous
  • reactivation
  • HHV-7 and HHV-6 reactivation associated with pityriasis rosea (Drago, 1997 and Yasukawa, 1999)
  • Debated
    • Innocent bystander?
    • Multiple agents?

4.

  • Drug Reaction Eosinophilia and Systemic side effect Syndrome (DRESS)
  • HHV 6 reactivation (Deschamps 2001)
  • exanthema,hepatitis, colitis lymphadenopathy, eosinophilia, fever
  • EBV and amoxicillin associated drug rash in mononucleosis infectiosa

C Goldberg, UCSD and Ascend Media Healthcare 5. Ascend Media Healthcare 6.

  • Highest prevalence in over 50 year olds
  • Self limiting
  • Normally one episode
  • Association with HCV (Mokni 1991)
    • The epidemiological association is not strong (Imhof, 1997)

7. Electron microscopy oflichen planus lesional skin lichen planus lichen planus lichen planus reference herpes virus 8.

  • Objective :
    • To find candidate herpes viruses associated with lichen planus.
  • Methods :
    • Lichen planus patients (pathologically confirmed, n=18)
    • Intra patient comparison of skin biopsies:
      • lesional vs. non-lesional
      • before vs. after remission
    • Inter patient comparison of skin biopsies:
      • psoriasis patients (lesional, n=11, and non-lesional, n=3)
      • normal skin (redundant after breast reduction, n=4)
    • DNA of HSV1 and 2, VZV, CMV, EBV (commercial PCR )
    • DNA of HHV 6, -7 and -8 (in house nested PCR)

9. * p=0,06, # p=0,05 p values calculated with McNemar test

  • All samples were free of HSV-1, HSV-2, VZV, CMV and HHV-8 DNA.
  • EBV DNA was detected in 2/15 lichen planus lesional samples.

HHV7 HHV6 Lichen planus lesional non-lesional PBMC 11/18 (61%)* ,# 1/11(9%)* 5/13(38%) 0/18 (0%) 0/11 (0%) 2/13 (15%) Psoriasis lesional non-lesional 2/11(18%) # 0/3(0%) 1/11 (9%) 0/3(0%) Normal skin 0/4(0%) 0/4(0%) 10.

  • Immunohistochemical detection viral protein (HHV-7)
  • tegument protein pp85 (Advanced Biotechnologies)
  • positive cells/mm 2
  • (non) lesional lichen planus, psoriasis, normal skin

lesional skin non-lesional skin de Vries et al. Br J Dermatol 154: 361, 2006 11. psoriasislesional lichen planus normal skinnon lesional lichen planusde Vries et al. Br J Dermatol 154: 361, 2006- 12. lesional skin non-lesional skin CD123 positive cells(red), endothelial cells (blue) de Vries et al. Br J Dermatol 154: 361, 2006 13. HHV-7/BDCA-2 double staining HHV-7/CD-3 double staining lesional lichen planus lesional lichen planus de Vries et al. Arch Dermatol Res 299: 213, 2007 14. before treatment after remission de Vries et al. Arch Dermatol Res 299: 213, 2007 15.

  • herpes virus like particles reside in lesional lichen planus skin
  • not HSV1, HSV2, CMV, VZV, HHV6 or HHV8 DNA
  • HHV-7 replicates in lesional lichen planus,
  • not in non-lesional lichen planus, psoriatic or normal skin
  • HHV-7 replicatesin plasmacytoid dendritic cells
  • HHV-7 replication in lichen planus stops after remission

16.

  • HHV-7 (subclinical) primo infection during childhood
  • HHV-7 reactivation in adult life
  • replication in basal keratinocytes/dermal lymphocytes
  • presentation (plasmacytoid) dendritic cells
  • inflammatory T lymphocytic response
  • destruction of the basal layer

Skin Immune System, Bos JD ed. 3rd edition, 2005 17.

  • viral innocent bystander
  • Kochs postulates
  • g eographic variation in viral distribution
  • differences in laboratory protocols
  • virus-virus interactions
  • association with skin diseases?
  • or candidates in search of a disease?

18.

  • Jan van Marle
    • electronmicroscopy
  • Jan Weel
    • virology
  • Fokla Zorgdrager and Marion Cornelissen
    • molecular biology
  • Daisy Picavet and Marcel Teunissen
    • immunohistochemistry