Chromosomally integrated human herpesvirus 6: questions and answers

Philip E Pellett,Louis Flamand,Yasuko Mori,Katherine N Ward,Paolo Lusso,Agnès Gautheret‐Dejean,Rammurti T Kamble,Edward Seto,Caroline B Hall,Peter F Ambros,Irmeli Lautenschlager,Mary T Caserta,Kristin S Loomis,Peter G Medveczky,Henri Agut,Raymund R Razonable,Mario Luppi,Dharam V Ablashi,Tetsushi Yoshikawa,Uwe Kuehl,Masao Ogata,Dirk Laßner ,Joshua Pritchett ,José G Montoya ,V Descamps ,Sylvie Ranger-Rogez

doi:10.1002/rmv.715

Abstract

SUMMARYChromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.

Highlights

Supporting information can be found in the online version of this article Received: 9 August 2011; Revised: 2 September 2011; Accepted: 15 September 2011. This is a review of chromosomally integrated human herpesvirus 6 and its potential clinical implications (Table 1), in the form of a series of questions and answers
We provide a list of research questions (Table 3) to motivate studies that will allow more extensive evidencebased guidance to be offered in several years
HHV-6B can integrate into the chromosomes; of 34 published examples for which integration sites were mapped, 9 (26%) were HHV-6A and 25 (74%) were HHV-6B

Summary

SUMMARY

Integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. Supporting information can be found in the online version of this article Received: 9 August 2011; Revised: 2 September 2011; Accepted: 15 September 2011

INTRODUCTION

Findings

Key points