Chromosomally integrated human herpesvirus 6: Questions and answers

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

Research output: Contribution to journalReview article

185 Citations (Scopus)

Abstract

Chromosomally 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.

Original languageEnglish
Pages (from-to)144-155
Number of pages12
JournalReviews in Medical Virology
Volume22
Issue number3
DOIs
Publication statusPublished - 01-05-2012

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Human Herpesvirus 6
DNA
Genome
Immune Tolerance
Graft Rejection
Viral Proteins
Bacterial Infections
Germ Cells
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Pellett, P. E., Ablashi, D. V., Ambros, P. F., Agut, H., Caserta, M. T., Descamps, V., ... Razonable, R. R. (2012). Chromosomally integrated human herpesvirus 6: Questions and answers. Reviews in Medical Virology, 22(3), 144-155. https://doi.org/10.1002/rmv.715
Pellett, Philip E. ; Ablashi, Dharam V. ; Ambros, Peter F. ; Agut, Henri ; Caserta, Mary T. ; Descamps, Vincent ; Flamand, Louis ; Gautheret-Dejean, Agnès ; Hall, Caroline B. ; Kamble, Rammurti T. ; Kuehl, Uwe ; Lassner, Dirk ; Lautenschlager, Irmeli ; Loomis, Kristin S. ; Luppi, Mario ; Lusso, Paolo ; Medveczky, Peter G. ; Montoya, Jose G. ; Mori, Yasuko ; Ogata, Masao ; Pritchett, Joshua C. ; Rogez, Sylvie ; Seto, Edward ; Ward, Katherine N. ; Yoshikawa, Tetsushi ; Razonable, Raymund R. / Chromosomally integrated human herpesvirus 6 : Questions and answers. In: Reviews in Medical Virology. 2012 ; Vol. 22, No. 3. pp. 144-155.
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Pellett, PE, Ablashi, DV, Ambros, PF, Agut, H, Caserta, MT, Descamps, V, Flamand, L, Gautheret-Dejean, A, Hall, CB, Kamble, RT, Kuehl, U, Lassner, D, Lautenschlager, I, Loomis, KS, Luppi, M, Lusso, P, Medveczky, PG, Montoya, JG, Mori, Y, Ogata, M, Pritchett, JC, Rogez, S, Seto, E, Ward, KN, Yoshikawa, T & Razonable, RR 2012, 'Chromosomally integrated human herpesvirus 6: Questions and answers', Reviews in Medical Virology, vol. 22, no. 3, pp. 144-155. https://doi.org/10.1002/rmv.715

Chromosomally integrated human herpesvirus 6 : Questions and answers. / Pellett, Philip E.; Ablashi, Dharam V.; Ambros, Peter F.; Agut, Henri; Caserta, Mary T.; Descamps, Vincent; Flamand, Louis; Gautheret-Dejean, Agnès; Hall, Caroline B.; Kamble, Rammurti T.; Kuehl, Uwe; Lassner, Dirk; Lautenschlager, Irmeli; Loomis, Kristin S.; Luppi, Mario; Lusso, Paolo; Medveczky, Peter G.; Montoya, Jose G.; Mori, Yasuko; Ogata, Masao; Pritchett, Joshua C.; Rogez, Sylvie; Seto, Edward; Ward, Katherine N.; Yoshikawa, Tetsushi; Razonable, Raymund R.

In: Reviews in Medical Virology, Vol. 22, No. 3, 01.05.2012, p. 144-155.

Research output: Contribution to journalReview article

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AU - Pellett, Philip E.

AU - Ablashi, Dharam V.

AU - Ambros, Peter F.

AU - Agut, Henri

AU - Caserta, Mary T.

AU - Descamps, Vincent

AU - Flamand, Louis

AU - Gautheret-Dejean, Agnès

AU - Hall, Caroline B.

AU - Kamble, Rammurti T.

AU - Kuehl, Uwe

AU - Lassner, Dirk

AU - Lautenschlager, Irmeli

AU - Loomis, Kristin S.

AU - Luppi, Mario

AU - Lusso, Paolo

AU - Medveczky, Peter G.

AU - Montoya, Jose G.

AU - Mori, Yasuko

AU - Ogata, Masao

AU - Pritchett, Joshua C.

AU - Rogez, Sylvie

AU - Seto, Edward

AU - Ward, Katherine N.

AU - Yoshikawa, Tetsushi

AU - Razonable, Raymund R.

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N2 - Chromosomally 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.

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Pellett PE, Ablashi DV, Ambros PF, Agut H, Caserta MT, Descamps V et al. Chromosomally integrated human herpesvirus 6: Questions and answers. Reviews in Medical Virology. 2012 May 1;22(3):144-155. https://doi.org/10.1002/rmv.715