What is new on HHV 6, 7, 8 infections?

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What is new on HHV 6, 7, 8 infections?. Henry J.C. de Vries Dermatology Academic Medical Centre University of Amsterdam The Netherlands. HHV 6 and 7 Acute/primary infection. Until 1986, 5 herpes viruses new human herpes viruses (HHV) HHV-6 and -7 - PowerPoint PPT Presentation

Transcript of What is new on HHV 6, 7, 8 infections?

  • Henry J.C. de Vries Dermatology Academic Medical CentreUniversity of Amsterdam The Netherlands

  • Until 1986, 5 herpes virusesnew human herpes viruses (HHV)HHV-6 and -7 both members of the Roseolovirus genus of the -herpesviruses. T-lymphotropic but can infect other cell typesprimary infections are associated with roseola infantum (a.k.a. exanthem subitum or 6th disease)

  • HHV lifetime infectionubiquitousreactivationHHV-7 and HHV-6 reactivation associated with pityriasis rosea (Drago, 1997 and Yasukawa, 1999)DebatedInnocent 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 infectiosaC Goldberg, UCSD and Ascend Media Healthcare

  • Ascend Media Healthcare

  • Highest prevalence in over 50 year oldsSelf limitingNormally one episode

    Association with HCV (Mokni 1991)The epidemiological association is not strong (Imhof, 1997)

  • Electron microscopy of lichen planus lesional skinlichen planuslichen planuslichen planusreference 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)

  • * 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.

    HHV7HHV6Lichen planus lesional non-lesional PBMC11/18 (61%)*,#1/11 (9%)*5/13 (38%)0/18 (0%)0/11 (0%)2/13 (15%)Psoriasis lesional non-lesional2/11 (18%)#0/3 (0%)1/11 (9%)0/3 (0%)Normal skin0/4 (0%)0/4 (0%)

  • 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 skinnon-lesional skin

    CD123 positive cells(red), endothelial cells (blue)

    de Vries et al. Br J Dermatol 154: 361, 2006

  • HHV-7/BDCA-2 double stainingHHV-7/CD-3 double staininglesional lichen planuslesional lichen planusde Vries et al. Arch Dermatol Res 299: 213, 2007

  • before treatmentafter remissionde Vries et al. Arch Dermatol Res 299: 213, 2007

    Figure

    16.23.369.813.313.72.233.712.2

    #

    *

    before treatment

    after remission

    before treatment

    after remission

    epidermis dermis

    HHV-7 protein positive cells/mm(2)

    Data for figure

    HHV-7 immunohistochemical stained positive cells/ mm2

    epidermisdermis

    before treatmentafter remissionbefore treatmentafter remission

    mean16.23.369.813.3

    sd13.72.233.712.2

    Blad2

    Blad3

  • 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 childhoodHHV-7 reactivation in adult lifereplication in basal keratinocytes/dermal lymphocytespresentation (plasmacytoid) dendritic cellsinflammatory T lymphocytic responsedestruction of the basal layer Skin Immune System, Bos JD ed. 3rd edition, 2005

  • viral innocent bystanderKochs postulates geographic variation in viral distributiondifferences in laboratory protocolsvirus-virus interactions

    association with skin diseases?or candidates in search of a disease?

  • Jan van MarleelectronmicroscopyJan WeelvirologyFokla Zorgdrager and Marion Cornelissenmolecular biologyDaisy Picavet and Marcel Teunissenimmunohistochemistry

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