Leading HHV-6 investigators encourage using new name for iciHHV6

In All, ciHHV-6, iciHHV-6 by Kristin Loomis

Read why some believe that "endogenous HHV-6" is a better term than inherited chromosomally integrated HHV-6, and sign on to their open letter if you agree.

Following discussions at the Himeji Conference, a group of investigators have concluded that it would reduce confusion in future publications if the community of investigators agreed to adopt the term “endogenous HHV-6” to refer to inherited chromosomally integrated HHV-6A/B.

A letter explaining the rationale for this decision will be sent to the Journal of Virology.  The text of the letter is copied below. 

If you would like to sign this letter, please use the link below to confirm that we can add your name to the list of investigators supporting this change.

https://forms.gle/fBB7GZYeJ2FLgmUk7

Letter supporting a name change for inherited chromosomally integrated HHV-6:

The integrated HHV-6A/B can reactivate, express their genes and even produce infectious progeny, as isolation of infectious virus identical in sequence to the endogenous HHV-6 has been reported (10-13). Viral DNA integration therefore represents one way to achieve latency: the more conventional means of achieving latency in herpesviruses, episomal viral DNA, has not yet been demonstrated or characterized.

Depending on ancestry (and geographic region), between 0.2 and 3% of humans carry such endogenous HHV-6A/B (14-18). The possible health consequences of this viral DNA inheritance, and the implications for medical practice, are the subject of active investigation (19).  Preliminary evidence suggests the condition may increase the risk for angina pectoris (17), preeclampsia (20), and systemic lupus erythematosus (18).

Authors have used different names for this phenomenon including “chromosomally integrated HHV-6 (or ciHHV-6)”, “inherited chromosomally integrated HHV-6 (or iciHHV-6)” or, more recently, “endogenous HHV-6 (eHHV-6)” (4, 18). This has created confusion in the literature.

To avoid such confusion, the undersigned authors of this letter, who study HHV-6A/B, urge that all investigators adopt a consistent term—"endogenous HHV-6A/B (eHHV-6A/B)”—when referring to inherited HHV-6A/B DNA. At least for the next few years, after using the term for the first time in a manuscript, authors should add a parenthetical “(previously called ciHHV-6 or iciHHV-6)”, for clarification. The term eHHV-6A/B is simpler and shorter. It also is clearer, since virologists and many health care providers and biomedical scientists are familiar with the term “endogenous retroviral DNA”.

Similarly, the term “ciHHV-6” should be used only to describe somatic chromosomal integrations.

The undersigned commit ourselves to using this terminology exclusively, henceforth.

Louis Flamand, Joshua A. Hill, Ruth Jarrett, Benedikt B. Kaufer, Anthony L. Komaroff, Yasuko Mori, Nicholas Parrish, Philip E. Pellett, Michael Wood, Tetsushi Yoshikawa….. and the additional undersigned authors (listed online in the Supplementary Information for this Letter).

References

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  2. Hill JA, Koo S, Guzman Suarez BB, Ho VT, Cutler C, Koreth J, et al. Cord-blood hematopoietic stem-cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: A cohort analysis. Biol Blood Marrow Transplant. 2012;18(11):1638-48.
  3. Ogata M, Satou T, Inoue Y, Takano K, Ikebe T, Ando T, et al. Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis. Bone Marrow Transplant. 2013;48(2):257-64.
  4. Aswad A, Aimola G, Wight D, Roychoudhury P, Zimmermann C, Hill J, et al. Evolutionary history of endogenous human herpesvirus 6 reflects human migration out of Africa. Mol Biol Evol. 2021;38(1):96-107.
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  7. Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci U S A. 2010;107(12):5563-8.
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  9. Wight DJ, Aimola G, Aswad A, Jill Lai CY, Bahamon C, Hong K, et al. Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6. Proc Natl Acad Sci U S A. 2020;117(49):31410-6.
  10. Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, et al. Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency. Clin Infect Dis. 2014;59(4):545-8.
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  13. Hannolainen L, Pyoria L, Pratas D, Lohi J, Skuja S, Rasa-Dzelzkaleja S, et al. Reactivation of a transplant recipient's inherited human herpesvirus 6 and implications to the graft. J Infect Dis. 2025;231(2):e267-e76.
  14. Leong HN, Tuke PW, Tedder RS, Khanom AB, Eglin RP, Atkinson CE, et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol. 2007;79(1):45-51.
  15. Potenza L, Barozzi P, Masetti M, Pecorari M, Bresciani P, Gautheret-Dejean A, et al. Prevalence of human herpesvirus-6 chromosomal integration (CIHHV-6) in Italian solid organ and allogeneic stem cell transplant patients. Am J Transplant. 2009;9(7):1690-7.
  16. Hubacek P, Muzikova K, Hrdlickova A, Cinek O, Hyncicova K, Hrstkova H, et al. Prevalence of HHV-6 integrated chromosomally among children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic. J Med Virol. 2009;81(2):258-63.
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