What is new on HHV 6,7,8 infections?, Henry J.C. de Vries
-
Upload
prezi22 -
Category
Health & Medicine
-
view
993 -
download
1
description
Transcript of What is new on HHV 6,7,8 infections?, Henry J.C. de Vries
Henry J.C. de Vries
Dermatology
Academic Medical Centre
University of Amsterdam
The Netherlands
Until 1986, 5 herpes viruses new human herpes viruses
(HHV) HHV-6 and -7
• both members of the Roseolovirus genus of the β-herpesviruses.
• T-lymphotropic but can infect other cell types
• primary infections are associated with roseola infantum (a.k.a. exanthem subitum or 6th disease)
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?
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
Ascend Media Healthcare
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)
Electron microscopy of lichen planus lesional skin
lichen planus lichen planus
lichen planus reference herpes virus
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)
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%)* 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.
Immunohistochemical detection viral protein (HHV-7) tegument protein pp85 (Advanced Biotechnologies) positive cells/mm2
(non) lesional lichen planus, psoriasis, normal skin
lesional skin non-lesional skinde Vries et al. Br J Dermatol 154: 361, 2006
psoriasis lesional lichen planusnormal skin non lesional lichen planus
de Vries et al. Br J Dermatol 154: 361, 2006
-
lesional skin non-lesional skin
CD123 positive cells(red), endothelial cells (blue)
de Vries et al. Br J Dermatol 154: 361, 2006
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
before treatment after remission
de Vries et al. Arch Dermatol Res 299: 213, 2007
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 replicates in plasmacytoid dendritic cells
HHV-7 replication in lichen planus stops after remission
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
viral “innocent bystander” Koch’s postulates geographic variation in viral
distribution differences in laboratory protocols virus-virus interactions
association with skin diseases? or candidates in search of a disease?
Jan van Marle• electronmicroscopy
Jan Weel• virology
Fokla Zorgdrager and Marion Cornelissen• molecular biology
Daisy Picavet and Marcel Teunissen• immunohistochemistry