Download 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 βherpesviruses.
• 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)
•
•
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
0/4 (0%)
(0%)
* p=0,06, # p=0,05 p values calculated with McNemar test
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 skin
de Vries et al. Br J Dermatol 154: 361, 2006
-
psoriasis
normal skin
lesional lichen planus
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
lesional lichen planus
lesional lichen planus
HHV-7/BDCA-2 double staining
HHV-7/CD-3 double staining
de Vries et al. Arch Dermatol Res 299: 213, 2007
120
*
HHV-7 protein positive cells/mm(2)
100
80
60
40
#
20
0
epidermis
before treatment
dermis
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