human herpesvirus 6 epidemiology and disease associations Ruth Jarrett MRCUniversity of Glasgow Centre for Virus Research Human herpesvirus 6 Two distinct but closely related herpesviruses HHV6A and HHV6B ID: 927583
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Slide1
Inherited
chromosomally-integrated human herpesvirus 6: epidemiology and disease associations
Ruth JarrettMRC-University of Glasgow Centre for Virus Research
Slide2Human herpesvirus 6
Two distinct but closely related herpesviruses – HHV-6A and HHV-6BMost individuals are infected in early childhood
Virus persists for life and can be reactivatedHHV-6B more prevalent in Europe, the USA and JapanHHV-6A relatively more common in Africa?
Slide3HHV-6 and disease
Primary infection by HHV-6B causes roseola infantum and common cause of febrile seizuresReactivation rarely problematic in immunocompetent individuals
In immunosuppressed individuals reactivation is associated with encephalitis, colitis, hepatitis etc.Many other associations – mesial temporal lobe epilepsy, MS, myocarditis and cardiomyopathy, low Bayley scores – reported but not proven
Slide4HHV-6 integrates into telomeres
Direct repeat (DR)
Direct repeat (DR)
Unique region
162 kb of herpesvirus genome integrated
in telomere
Ho
mologous recombination
Host telomere
P
erfect and imperfect
t
elomere-like repeats
P
erfect and imperfect
t
elomere-like repeats
Slide5Integrated HHV-6 can be excised
Chromosomally integrated HHV-6
can reactivate in vivo
Excised viral genomes detected
in vitro
Chromosomally integrated HHV-6 may be a form of latent viral infection
Slide6Exogenous HHV-6 infection
?
Non-heritable
Inherited HHV-6 (iciHHV-6)
HHV-6 DNA
Heritable
HHV-6 DNA
Slide7Sudden telomere
shortening
Influence on expression of sub-telomeric genes
Inflammation
Senescence
Telomere fusion
Altered cellular gene expression
Chromosome-specific
Viral reactivation
Drugs
HDAC inhibitors
Slide8Inherited HHV-6 (iciHHV-6)
HHV-6 DNA
Heritable
Consequences of iciHHV-6?
Viral reactivation
Age-related disease
Cancer
Slide9iciHHV-6 in GS:SFHS: Aims
To explore clinical relevanceTo determine the prevalence of iciHHV-6 in a large population-based study
determine whether HHV-6A or HHV-6BTo determine whether chromosomal integration is randomTo analyse viral evolution evidence of new integrations
timing of integration events
Slide10Detection of iciHHV-6 in the GS:SFHS
Slide11Conclusions
Analysis of iciHHV-6 in the GS:SFHS has uncovered some unexpected findingsRegional differences in the iciHHV-6 prevalence in the UK were detected
iciHHV-6 is associated with an increased risk of some disease symptoms
Slide12Acknowledgements
University of GlasgowCVRAdam Bell
Chris BrownlieSkye StorrieAndrew DavisonRob Gifford
ICAMSChristian DellesBarts Health NHS TrustDuncan ClarkBGS, ICR
Anthony Swerdlow
Nick Orr
Archie Campbell
Caroline Hayward
Carmen Amador
Shona Kerr
Pamela Linksted
David J Porteous
Blair H Smith
Lynne Hocking
Sandosh Padmanabhan
Edinburgh Clinical Research Facility
Lee Murphy
Angie Fawkes