what is new on hhv 6,7,8 infections?, henry j.c. de vries
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Henry J.C. de Vries
Dermatology
Academic Medical Centre
University of Amsterdam
The Netherlands
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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)
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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?
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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
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Ascend Media Healthcare
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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)
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Electron microscopy of lichen planus lesional skin
lichen planus lichen planus
lichen planus reference herpes virus
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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)
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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.
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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
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psoriasis lesional lichen planusnormal skin non lesional lichen planus
de Vries et al. Br J Dermatol 154: 361, 2006
-
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lesional skin non-lesional skin
CD123 positive cells(red), endothelial cells (blue)
de Vries et al. Br J Dermatol 154: 361, 2006
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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
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before treatment after remission
de Vries et al. Arch Dermatol Res 299: 213, 2007
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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
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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
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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?
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Jan van Marle• electronmicroscopy
Jan Weel• virology
Fokla Zorgdrager and Marion Cornelissen• molecular biology
Daisy Picavet and Marcel Teunissen• immunohistochemistry