1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Human Herpesviruses 6A, 6B, and 7

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • PDF
    2.19 MB
  • HTML
    175.66 Kb
  • XML
    174.01 Kb
  • Authors: Henri Agut1,2,3, Pascale Bonnafous4,5, Agnès Gautheret-Dejean6,7,8,9
  • Editors: Randall T. Hayden10, Donna M. Wolk11, Karen C. Carroll12, Yi-Wei Tang13
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 2: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 3: AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France; 4: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 5: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 6: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France; 7: INSERM, CIMI-Paris U1135, PVI Team, Paris, France; 8: AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France; 9: Université René Descartes, Faculté de Pharmacie, Laboratoire de Microbiologie UPRES EA 4065, Paris, France; 10: Clinical and Molecular Microbiology, Department of Pathology, St. Jude’s Children’s Research Hospital, Memphis, TN; 11: Geisinger Clinic, Department of Laboratory Medicine, Danville, PA; 12: Johns Hopkins University Hospital, Baltimore, MD; 13: Clinical Microbiology Service, Memorial Sloane-Kettering Institute, New York, NY
    • Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
  • Received 15 March 2015 Accepted 15 June 2015 Published 17 June 2016
  • Henri Agut, [email protected]
image of Human Herpesviruses 6A, 6B, and 7
    Preview this microbiology spectrum article:
    Preview Magnify
    Zoom in
    Zoomout

    Human Herpesviruses 6A, 6B, and 7, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/4/3/DMIH2-0007-2015-1.gif /docserver/preview/fulltext/microbiolspec/4/3/DMIH2-0007-2015-2.gif

  • Abstract:

    Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.

  • Citation: Agut H, Bonnafous P, Gautheret-Dejean A. 2016. Human Herpesviruses 6A, 6B, and 7. Microbiol Spectrum 4(3):DMIH2-0007-2015. doi:10.1128/microbiolspec.DMIH2-0007-2015.

References

1. Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, Halligan G, Biberfeld P, Wong-Staal F, Kramarsky B, Gallo RC. 1986. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234:596–601. [PubMed][CrossRef]
2. Ablashi D, Agut H, Berneman Z, Campadelli-Fiume G, Carrigan D, Ceccerini-Nelli L, Chandran B, Chou S, Collandre H, Cone R, Dambaugh T, Dewhurst S, DiLuca D, Foa-Tomasi L, Fleckenstein B, Frenkel N, Gallo RC, Gompels UA, Hall C, Jones M, Lawrence G, Martin M, Montagnier L, Neipel F, Nicholas J, Pellett PE, Razzaque A, Torrelli G, Thomson B, Salahuddin SZ, Wyatt L, Yamanishi K. 1993. Human herpesvirus-6 strain groups: a nomenclature. Arch Virol 129:363–366. [CrossRef]
3. Ablashi D, Agut H, Alvarez-Lafuente R, Clark DA, Dewhurst S, DiLuca D, Flamand L, Frenkel N, Gallo R, Gompels UA, Höllsberg P, Jacobson S, Luppi M, Lusso P, Malnati M, Medveczky P, Mori Y, Pellett PE, Pritchett JC, Yamanishi K, Yoshikawa T. 2014. Classification of HHV-6A and HHV-6B as distinct viruses. Arch Virol 159:863–870. [PubMed][CrossRef]
4. Frenkel N, Schirmer EC, Wyatt LS, Katsafanas G, Roffman E, Danovich RM, June CH. 1990. Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci U S A 87:748–752. [PubMed][CrossRef]
5. De Bolle L, Naesens L, De Clercq E. 2005. Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev 18:217–245. [PubMed][CrossRef]
6. Braun DK, Dominguez G, Pellett PE. 1997. Human herpesvirus 6. Clin Microbiol Rev 10:521–567. [PubMed]
7. Flamand L, Komaroff AL, Arbuckle JH, Medveczky PG, Ablashi DV. 2010. Review, part 1: human herpesvirus-6-basic biology, diagnostic testing, and antiviral efficacy. J Med Virol 82:1560–1568. [PubMed][CrossRef]
8. Yamanishi K, Mori Y, Pellett PE. 2013. Human herpesviruses 6 and 7, p 2058–2079. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed), Fields Virology, 6 th ed, vol 2. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, PA.
9. Agut H, Bonnafous P, Gautheret-Dejean A. 2015. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev 28:313–335. [PubMed][CrossRef]
10. Achour A, Malet I, Le Gal F, Deheé A, Gautheret-Dejean A, Bonnafous P, Agut H. 2008. Variability of gB and gH genes of human herpesvirus-6 among clinical specimens. J Med Virol 80:1211–1221. [PubMed][CrossRef]
11. Gravel A, Hall CB, Flamand L. 2013. Sequence analysis of transplacentally acquired human herpesvirus 6 DNA is consistent with transmission of a chromosomally integrated reactivated virus. J Infect Dis 207:1585–1589. [PubMed][CrossRef]
12. Franti M, Aubin JT, Gautheret-Dejean A, Malet I, Cahour A, Huraux JM, Agut H. 1999. Preferential associations of alleles of three distinct genes argue for the existence of two prototype variants of human herpesvirus 7. J Virol 73:9655–9658. [PubMed]
13. Franti M, Gessain A, Darlu P, Gautheret-Dejean A, Kosuge H, Mauclère P, Aubin JT, Gurtsevitch V, Yamanishi K, Agut H. 2001. Genetic polymorphism of human herpesvirus-7 among human populations. J Gen Virol 82:3045–3050. [PubMed][CrossRef]
14. Santoro F, Kennedy PE, Locatelli G, Malnati MS, Berger EA, Lusso P. 1999. CD46 is a cellular receptor for human herpesvirus 6. Cell 99:817–827. [CrossRef]
15. Tang H, Serada S, Kawabata A, Ota M, Hayashi E, Naka T, Yamanishi K, Mori Y. 2013. CD134 is a cellular receptor specific for human herpesvirus-6B entry. Proc Natl Acad Sci U S A 110:9096–9099. [PubMed][CrossRef]
16. Lusso P, Secchiero P, Crowley RW, Garzino-Demo A, Berneman ZN, Gallo RC. 1994. CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proc Natl Acad Sci U S A 91:3872–3876. [PubMed][CrossRef]
17. Luppi M, Barozzi P, Marasca R, Torelli G. 1994. Integration of human herpesvirus-6 (HHV-6) genome in chromosome 17 in two lymphoma patients. Leukemia 8(Suppl 1) :S41–S45. [PubMed]
18. 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. Rev Med Virol 22:144–155. [PubMed][CrossRef]
19. Kaufer BB, Flamand L. 2014. Chromosomally integrated HHV-6: impact on virus, cell and organismal biology. Curr Opin Virol 9:111–118. [PubMed][CrossRef]
20. Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, Lund TC, Tolar J, De Meirleir K, Montoya JG, Komaroff AL, Ambros PF, Medveczky PG. 2010. 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 107:5563–5568. [PubMed][CrossRef]
21. Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, Kurahashi H, Yoshikawa T, Katano H, Inoue N, Imai K, Takagi M, Morio T, Mizutani S. 2014. 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 59:545–548. [PubMed][CrossRef]
22. Dewin DR, Catusse J, Gompels UA. 2006. Identification and characterization of U83A viral chemokine, a broad and potent beta-chemokine agonist for human CCRs with unique selectivity and inhibition by spliced isoform. J Immunol 176:544–556. [PubMed][CrossRef]
23. Catusse J, Spinks J, Mattick C, Dyer A, Laing K, Fitzsimons C, Smit MJ, Gompels UA. 2008. Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes. Eur J Immunol 38:763–777. [PubMed][CrossRef]
24. Lusso P, Gallo RC. 1995. Human herpesvirus 6 in AIDS. Immunol Today 16:67–71. [CrossRef]
25. Flamand L, Menezes J. 1996. Cyclic AMP-responsive element-dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6. J Virol 70:1784–1791. [PubMed]
26. Becerra A, Gibson L, Stern LJ, Calvo-Calle JM. 2014. Immune response to HHV-6 and implications for immunotherapy. Curr Opin Virol 9C:154–161. [PubMed][CrossRef]
27. Nastke MD, Becerra A, Yin L, Dominguez-Amorocho O, Gibson L, Stern LJ, Calvo-Calle JM. 2012. Human CD4+ T cell response to human herpesvirus 6. J Virol 86:4776–4792. [PubMed][CrossRef]
28. Gerdemann U, Keukens L, Keirnan JM, Katari UL, Nguyen CT, de Pagter AP, Ramos CA, Kennedy-Nasser A, Gottschalk SM, Heslop HE, Brenner MK, Rooney CM, Leen AM. 2013. Immunotherapeutic strategies to prevent and treat human herpesvirus 6 reactivation after allogeneic stem cell transplantation. Blood 121:207–218. [PubMed][CrossRef]
29. Tesini BL, Epstein LG, Caserta MT. 2014. Clinical impact of primary infection with roseoloviruses. Curr Opin Virol 9C:91–96. [PubMed][CrossRef]
30. Ward KN, Gray JJ, Efstathiou S. 1989. Brief report: primary human herpesvirus 6 infection in a patient following liver transplantation from a seropositive donor. J Med Virol 28:69–72. [PubMed][CrossRef]
31. Kusuhara K, Takabayashi A, Ueda K, Hidaka Y, Minamishima I, Take H, Fujioka K, Imai S, Osato T. 1997. Breast milk is not a significant source for early Epstein-Barr virus or human herpesvirus 6 infection in infants: a seroepidemiologic study in 2 endemic areas of human T-cell lymphotropic virus type I in Japan. Microbiol Immunol 41:309–312. [PubMed][CrossRef]
32. Hall CB, Caserta MT, Schnabel K, Shelley LM, Marino AS, Carnahan JA, Yoo C, Lofthus GK, McDermott MP. 2008. Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics 122:513–520. [PubMed][CrossRef]
33. Hall CB, Caserta MT, Schnabel KC, Shelley LM, Carnahan JA, Marino AS, Yoo C, Lofthus GK. 2010. Transplacental congenital human herpesvirus 6 infection caused by maternal chromosomally integrated virus. J Infect Dis 201:505–507. [PubMed][CrossRef]
34. Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, Knott A, Dewhurst S, Insel RA, Epstein LG. 1994. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med 331:432–438. [PubMed][CrossRef]
35. Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T. 1988. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1:1065–1067. [CrossRef]
36. Descamps V, Tohyama M, Kano Y, Shiohara T. 2014. HHV-6A and HHV-6B in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, p 179–200. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7. Elsevier, New York, NY.
37. Al-Zubeidi D, Thangarajh M, Pathak S, Cai C, Schlaggar BL, Storch GA, Grange DK, Watson ME Jr. 2014. Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders. Pediatr Neurol 51:448–452. [PubMed][CrossRef]
38. Ward KN, Andrews NJ, Verity CM, Miller E, Ross EM. 2005. Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland. Arch Dis Child 90:619–623. [PubMed][CrossRef]
39. Schwartz KL, Richardson SE, Ward KN, Donaldson C, MacGregor D, Banwell B, Mahant S, Bitnun A. 2014. Delayed primary HHV-7 infection and neurologic disease. Pediatrics 133:e1541–1547.
40. Yao K, Crawford JR, Komaroff AL, Ablashi DV, Jacobson S. 2010. Review part 2: human herpesvirus-6 in central nervous system diseases. J Med Virol 82:1669–1678. [PubMed][CrossRef]
41. Donati D, Akhyani N, Fogdell-Hahn A, Cermelli C, Cassiani-Ingoni R, Vortmeyer A, Heiss JD, Cogen P, Gaillard WD, Sato S, Theodore WH, Jacobson S. 2003. Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections. Neurology 61:1405–1411. [PubMed][CrossRef]
42. Epstein LG, Shinnar S, Hesdorffer DC, Nordli DR, Hamidullah A, Benn EK, Pellock JM, Frank LM, Lewis DV, Moshe SL, Shinnar RC, Sun S; FEBSTAT Study Team. 2012. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia 53:1481–1488. [PubMed][CrossRef]
43. Caserta MT, Hall CB, Canfield RL, Davidson P, Lofthus G, Schnabel K, Carnahan J, Shelley L, Wang H. 2014. Early developmental outcomes of children with congenital HHV-6 infection. Pediatrics 134:1111–1118. [PubMed][CrossRef]
44. Clark DA, Griffiths PD. 2003. Human herpesvirus 6: relevance of infection in the immunocompromised host. Br J Haematol 120:384–395. [PubMed][CrossRef]
45. Ogata M, Satou T, Kadota J, Saito N, Yoshida T, Okumura H, Ueki T, Nagafuji K, Kako S, Uoshima N, Tsudo M, Itamura H, Fukuda T. 2013. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis 57:671–681. [PubMed][CrossRef]
46. Zerr DM, Fann JR, Breiger D, Boeckh M, Adler AL, Xie H, Delaney C, Huang ML, Corey L, Leisenring WM. 2011. HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients. Blood 117:5243–5249. [PubMed][CrossRef]
47. Zerr DM, Ogata M. 2014. HHV-6A and HHV-6B in recipients of hematopoietic cell transplantation, p 217–234. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [CrossRef]
48. Luppi M, Barozzi P, Morris C, Maiorana A, Garber R, Bonacorsi G, Donelli A, Marasca R, Tabilio A, Torelli G. 1999. Human herpesvirus 6 latently infects early bone marrow progenitors in vivo. J Virol 73:754–759. [PubMed]
49. Gautheret-Dejean A, Dejean O, Vastel L, Kerboull M, Aubin JT, Franti M, Agut H. 2000. Human herpesvirus-6 and human herpesvirus-7 in the bone marrow from healthy subjects. Transplantation 69:1722–1723. [PubMed][CrossRef]
50. Boutolleau D, Fernandez C, André E, Imbert-Marcille BM, Milpied N, Agut H, Gautheret-Dejean A. 2003. Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. J Infect Dis 187:179–186. [PubMed][CrossRef]
51. Ward KN, White RP, Mackinnon S, Hanna M. 2002. Human herpesvirus-7 infection of the CNS with acute myelitis in an adult bone marrow recipient. Bone Marrow Transplant 30:983–985. [PubMed][CrossRef]
52. Fule Robles JD, Cheuk DK, Ha SY, Chiang AK, Chan GC. 2014. Human herpesvirus types 6 and 7 infection in pediatric hematopoietic stem cell transplant recipients. Ann Transplant 19:269–276. [PubMed][CrossRef]
53. Caïola D, Karras A, Flandre P, Boutolleau D, Scieux C, Agut H, Legendre C, Gautheret-Dejean A. 2012. Confirmation of the low clinical effect of human herpesvirus-6 and -7 infections after renal transplantation. J Med Virol 84:450–456. [PubMed][CrossRef]
54. Lautenschlager I, Razonable RR. 2014. HHV-6A and HHV-6B in solid organ transplantation, p 201–215. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [CrossRef]
55. Razonable RR. 2010. Infections due to human herpesvirus 6 in solid organ transplant recipients. Curr Opin Organ Transplant 15:671–675. [PubMed][CrossRef]
56. Humar A, Malkan G, Moussa G, Greig P, Levy G, Mazzulli T. 2000. Human herpesvirus-6 is associated with cytomegalovirus reactivation in liver transplant recipients. J Infect Dis 181:1450–1453. [PubMed][CrossRef]
57. Ablashi DV, Devin CL, Yoshikawa T, Lautenschlager I, Luppi M, Kühl U, Komaroff AL. 2010. Review Part 3: human herpesvirus-6 in multiple non-neurological diseases. J Med Virol 82:1903–1910. [PubMed][CrossRef]
58. Razonable RR. 2013. Human herpesviruses 6, 7 and 8 in solid organ transplant recipients. Am J Transplant 13(Suppl 3) :67–77; quiz 77–78. [PubMed][CrossRef]
59. Razonable RR, Zerr DM; AST Infectious Diseases Community of Practice. 2009. HHV-6, HHV-7 and HHV-8 in solid organ transplant recipients. Am J Transplant 9(Suppl 4) :S97–S100. [PubMed][CrossRef]
60. Yoshikawa T. 2003. Human herpesvirus-6 and -7 infections in transplantation. Pediatr Transplant 7:11–17. [PubMed][CrossRef]
61. Tong CY, Bakran A, Williams H, Cheung CY, Peiris JS. 2000. Association of human herpesvirus 7 with cytomegalovirus disease in renal transplant recipients. Transplantation 70:213–216. [PubMed]
62. Griffiths PD, Ait-Khaled M, Bearcroft CP, Clark DA, Quaglia A, Davies SE, Burroughs AK, Rolles K, Kidd IM, Knight SN, Noibi SM, Cope AV, Phillips AN, Emery VC. 1999. Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus. J Med Virol 59:496–501. [PubMed][CrossRef]
63. Corbellino M, Lusso P, Gallo RC, Parravicini C, Galli M, Moroni M. 1993. Disseminated human herpesvirus 6 infection in AIDS. Lancet 342:1242. [PubMed][CrossRef]
64. Gautheret A, Aubin JT, Fauveau V, Rozenbaum W, Huraux JM, Agut H. 1995. Rate of detection of human herpesvirus-6 at different stages of HIV infection. Eur J Clin Microbiol Infect Dis 14:820–824. [PubMed][CrossRef]
65. Lusso P, Gallo RC. 1994. Human herpesvirus 6 in AIDS. Lancet 343:555–556. [CrossRef]
66. Spira TJ, Bozeman LH, Sanderlin KC, Warfield DT, Feorino PM, Holman RC, Kaplan JE, Fishbein DB, Lopez C. 1990. Lack of correlation between human herpesvirus-6 infection and the course of human immunodeficiency virus infection. J Infect Dis 161:567–570. [PubMed][CrossRef]
67. Knox KK, Harrington DP, Carrigan DR. 1995. Fulminant human herpesvirus six encephalitis in a human immunodeficiency virus-infected infant. J Med Virol 45:288–292. [PubMed][CrossRef]
68. Fillet AM, Reux I, Joberty C, Fournier JG, Hauw JJ, Le Hoang P, Bricaire F, Huraux JM, Agut H. 1996. Detection of human herpes virus 6 in AIDS-associated retinitis by means of in situ hybridization, polymerase chain reaction and immunohistochemistry. J Med Virol 49:289–295. [CrossRef]
69. Hudson AW. 2014. Roseoloviruses and their modulation of host defenses. Curr Opin Virol 9C:178–187. [PubMed][CrossRef]
70. Descamps V, Bouscarat F, Laglenne S, Aslangul E, Veber B, Descamps D, Saraux JL, Grange MJ, Grossin M, Navratil E, Crickx B, Belaich S. 1997. Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome. Br J Dermatol 137:605–608. [PubMed][CrossRef]
71. Tohyama M, Yahata Y, Yasukawa M, Inagi R, Urano Y, Yamanishi K, Hashimoto K. 1998. Severe hypersensitivity syndrome due to sulfasalazine associated with reactivation of human herpesvirus 6. Arch Dermatol 134:1113–1117. [PubMed][CrossRef]
72. Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. 2007. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 156:1083–1084. [PubMed][CrossRef]
73. Yoshikawa T. 2014. HHV-6B and HHV-7 in exanthema subitum and related skin diseases, p 153–166. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, Third Edition. Elsevier, Amsterdam. [CrossRef]
74. Picard D, Janela B, Descamps V, D’Incan M, Courville P, Jacquot S, Rogez S, Mardivirin L, Moins-Teisserenc H, Toubert A, Benichou J, Joly P, Musette P. 2010. Drug reaction with eosinophilia and systemic symptoms (DRESS): a multiorgan antiviral T cell response. Sci Transl Med 2:46ra62. [PubMed][CrossRef]
75. Mardivirin L, Descamps V, Lacroix A, Delebassée S, Ranger-Rogez S. 2009. Early effects of drugs responsible for DRESS on HHV-6 replication in vitro. J Clin Virol 46:300–302. [PubMed][CrossRef]
76. Mardivirin L, Valeyrie-Allanore L, Branlant-Redon E, Beneton N, Jidar K, Barbaud A, Crickx B, Ranger-Rogez S, Descamps V. 2010. Amoxicillin-induced flare in patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on human herpesvirus 6 replication in vitro. Eur J Dermatol 20:68–73. [PubMed]
77. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A. 1997. Human herpesvirus 7 in pityriasis rosea. Lancet 349:1367–1368. [CrossRef]
78. Bezerra TM, Ferreira DC, Carmo FL, Pinheiro R, Leite DC, Cavalcante FS, Belinho RA, Peixoto RS, Rosado AS, dos Santos KR, Castro GF. 2015. Herpesvirus in the oral cavity of children with leukaemia and its impact on the oral bacterial community profile. J Clin Pathol 68:222–228. [PubMed][CrossRef]
79. Drago F, Javor S, Bruzzone L, Drago F, Parodi A, Picciotto A. 2014. Pityriasis rosea in a hepatitis B-positive patient treated with pegylated interferon α2a: report of a case and review of the literature. Dermatology 228:10–13. [PubMed][CrossRef]
80. Challoner PB, Smith KT, Parker JD, MacLeod DL, Coulter SN, Rose TM, Schultz ER, Bennett JL, Garber RL, Chang M, Schad PA, Stewart PM, Nowinski RC, Brown JP, Burmer GC. 1995. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A 92:7440–7444. [PubMed][CrossRef]
81. Leibovitch EC, Jacobson S. 2014. Evidence linking HHV-6 with multiple sclerosis: an update. Curr Opin Virol 9:127–133. [PubMed][CrossRef]
82. Merelli E, Bedin R, Sola P, Barozzi P, Mancardi GL, Ficarra G, Franchini G. 1997. Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children. J Neurol 244:450–454. [PubMed][CrossRef]
83. Liedtke W, Malessa R, Faustmann PM, Eis-Hübinger AM. 1995. Human herpesvirus 6 polymerase chain reaction findings in human immunodeficiency virus associated neurological disease and multiple sclerosis. J Neurovirol 1:253–258. [PubMed][CrossRef]
84. Cermelli C, Berti R, Soldan SS, Mayne M, D’Ambrosia JM, Ludwin SK, Jacobson S. 2003. High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection. J Infect Dis 187:1377–1387. [PubMed][CrossRef]
85. Virtanen JO, Pietiläinen-Nicklén J, Uotila L, Färkkilä M, Vaheri A, Koskiniemi M. 2011. Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid. J Neuroimmunol 237:93–97. [PubMed][CrossRef]
86. Caselli E, Boni M, Bracci A, Rotola A, Cermelli C, Castellazzi M, Di Luca D, Cassai E. 2002. Detection of antibodies directed against human herpesvirus 6 U94/REP in sera of patients affected by multiple sclerosis. J Clin Microbiol 40:4131–4137. [PubMed][CrossRef]
87. Broccolo F. 2014. HHV-6A and HHV-6B in autoimmune disease, p 167–178. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [CrossRef]
88. Caselli E, Zatelli MC, Rizzo R, Benedetti S, Martorelli D, Trasforini G, Cassai E, degli Uberti EC, Di Luca D, Dolcetti R. 2012. Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto’s thyroiditis. PLoS Pathog 8:e1002951. doi.10.1371/journal.ppat.1002951
89. Zerr DM, Komaroff AL. 2014. Cognitive dysfunction from HHV-6A and HHV-B, p. 99-122. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [CrossRef]
90. Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A, Ablashi DV, Salahuddin SZ, Saxinger C, Biddle R, Kikinis R, Jolesz FA, Folks T, Balachandran N, Peter JB, Gallo RC, Komaroff AL. 1992. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med 116:103–113. [PubMed][CrossRef]
91. Patnaik M, Komaroff AL, Conley E, Ojo-Amaize EA, Peter JB. 1995. Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome. J Infect Dis 172:1364–1367. [PubMed][CrossRef]
92. Ablashi DV, Zompetta C, Lease C, Josephs SF, Balachandra N, Komaroff AL, Krueger GR, Henry B, Lukau J, Salahuddin SZ. 1991. Human herpesvirus 6 (HHV6) and chronic fatigue syndrome (CFS). Can Dis Wkly Rep 17(Suppl 1E) :33–40. [PubMed]
93. Agut H, Aubin JT, Huraux JM. 1991. Homogeneous susceptibility of distinct human herpesvirus 6 strains to antivirals in vitro. J Infect Dis 163:1382–1383. [PubMed][CrossRef]
94. Pritchett JC, Naesens L, Montoya J. 2014. Treating HHV-6 infections: the laboratory efficacy and clinical use of anti-HHV-6 agents, p 311–331. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [PubMed][CrossRef]
95. Prichard MN, Whitley RJ. 2014. The development of new therapies for human herpesvirus 6. Curr Opin Virol 9:148–153. [PubMed][CrossRef]
96. Black JB, Pellett PE. 1999. Human herpesvirus 7. Rev Med Virol 9:245–262. [CrossRef]
97. De Clercq E, Naesens L, De Bolle L, Schols D, Zhang Y, Neyts J. 2001. Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8. Rev Med Virol 11:381–395. [PubMed][CrossRef]
98. Manichanh C, Olivier-Aubron C, Lagarde JP, Aubin JT, Bossi P, Gautheret-Dejean A, Huraux JM, Agut H. 2001. Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo. J Gen Virol 82:2767–2776. [PubMed][CrossRef]
99. Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H. 2007. Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther 12:877–888. [PubMed]
100. Bonnafous P, Boutolleau D, Naesens L, Deback C, Gautheret-Dejean A, Agut H. 2008. Characterization of a cidofovir-resistant HHV-6 mutant obtained by in vitro selection. Antiviral Res 77:237–240. [PubMed][CrossRef]
101. Safronetz D, Petric M, Tellier R, Parvez B, Tipples GA. 2003. Mapping ganciclovir resistance in the human herpesvirus-6 U69 protein kinase. J Med Virol 71:434–439. [PubMed][CrossRef]
102. Isegawa Y, Hara J, Amo K, Osugi Y, Takemoto M, Yamanishi K, Fukunaga R, Shibata M, Ohshima A, Horiguchi Y, Sugimoto N. 2009. Human herpesvirus 6 ganciclovir-resistant strain with amino acid substitutions associated with the death of an allogeneic stem cell transplant recipient. J Clin Virol 44:15–19. [PubMed][CrossRef]
103. Caserta MT, Dewhurst S. 2011. Dazed and confused by HHV-6. Blood 117:5016–5018. [PubMed][CrossRef]
104. Bonnafous P, Bogaert S, Godet AN, Agut H. 2013. HDP-CDV as an alternative for treatment of human herpesvirus-6 infections. J Clin Virol 56:175–176. [PubMed][CrossRef]
105. Naesens L, Bonnafous P, Agut H, De Clercq E. 2006. Antiviral activity of diverse classes of broad-acting agents and natural compounds in HHV-6-infected lymphoblasts. J Clin Virol 37(Suppl 1) :S69–S75. [CrossRef]
106. De Clercq E, Naesens L. 2006. In search of effective anti-HHV-6 agents. J Clin Virol 37(Suppl 1) :S82–S86. [CrossRef]
107. Milbradt J, Auerochs S, Korn K, Marschall M. 2009. Sensitivity of human herpesvirus 6 and other human herpesviruses to the broad-spectrum antiinfective drug artesunate. J Clin Virol 46:24–28. [PubMed][CrossRef]
108. Hakacova N, Klingel K, Kandolf R, Engdahl E, Fogdell-Hahn A, Higgins T. 2013. First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child. J Clin Virol 57:157–160. [PubMed][CrossRef]
109. Agut H. 2011. Deciphering the clinical impact of acute human herpesvirus 6 (HHV-6) infections. J Clin Virol 52:164–171. [PubMed][CrossRef]
110. Razonable RR, Hayden RT. 2013. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 26:703–727. [PubMed][CrossRef]
111. Agut H, Boutolleau D, Deback C, Bonnafous P, Gautheret-Dejean A. 2009. Testing the susceptibility of human herpesviruses to antivirals. Future Microbiol 4:1111–1123. [PubMed][CrossRef]
112. Gautheret-Dejean A, Agut H. 2014. Practical diagnostic procedures for HHV-6A, HHV-6B, and HHV-7, p 9–34. In Flamand L, Lautenschlager I, Krueger G, Ablashi D (ed), Human Herpesviruses HHV-6A, HHV-6B & HHV-7, 3rd ed. Elsevier, New York, NY. [CrossRef]
113. Descamps V, Avenel-Audran M, Valeyrie-Allanore L, Bensaid B, Barbaud A, Al Jawhari M, Ranger-Rogez S; French Study Group of Cutaneous Drug Adverse Reactions. 2013. Saliva polymerase chain reaction assay for detection and follow-up of herpesvirus reactivation in patients with drug reaction with eosinophilia and systemic symptoms (DRESS). JAMA Dermatol 149:565–569. [PubMed][CrossRef]
114. Asada H, Yalcin S, Balachandra K, Higashi K, Yamanishi K. 1989. Establishment of titration system for human herpesvirus 6 and evaluation of neutralizing antibody response to the virus. J Clin Microbiol 27:2204–2207. [PubMed]
115. Tsukazaki T, Yoshida M, Namba H, Yamada M, Shimizu N, Nii S. 1998. Development of a dot blot neutralizing assay for HHV-6 and HHV-7 using specific monoclonal antibodies. J Virol Methods 73:141–149. [PubMed][CrossRef]
116. Chou SW, Scott KM. 1990. Rises in antibody to human herpesvirus 6 detected by enzyme immunoassay in transplant recipients with primary cytomegalovirus infection. J Clin Microbiol 28:851–854. [PubMed]
117. Saxinger C, Polesky H, Eby N, Grufferman S, Murphy R, Tegtmeir G, Parekh V, Memon S, Hung C. 1988. Antibody reactivity with HBLV (HHV-6) in U.S. populations. J Virol Methods 21:199–208. [PubMed][CrossRef]
118. LaCroix S, Stewart JA, Thouless ME, Black JB. 2000. An immunoblot assay for detection of immunoglobulin M antibody to human herpesvirus 6. Clin Diagn Lab Immunol 7:823–827. [CrossRef]
119. Ward KN, Gray JJ, Joslin ME, Sheldon MJ. 1993. Avidity of IgG antibodies to human herpesvirus-6 distinguishes primary from recurrent infection in organ transplant recipients and excludes cross-reactivity with other herpesviruses. J Med Virol 39:44–49. [PubMed][CrossRef]
120. Black JB, Durigon E, Kite-Powell K, de Souza L, Curli SP, Afonso AM, Theobaldo M, Pellett PE. 1996. Seroconversion to human herpesvirus 6 and human herpesvirus 7 among Brazilian children with clinical diagnoses of measles or rubella. Clin Infect Dis 23:1156–1158. [PubMed][CrossRef]
121. Adler SP, McVoy M, Chou S, Hempfling S, Yamanishi K, Britt W. 1993. Antibodies induced by a primary cytomegalovirus infection react with human herpesvirus 6 proteins. J Infect Dis 168:1119–1126. [PubMed][CrossRef]
122. Sutherland S, Christofinis G, O’Grady J, Williams R. 1991. A serological investigation of human herpesvirus 6 infections in liver transplant recipients and the detection of cross-reacting antibodies to cytomegalovirus. J Med Virol 33:172–176. [PubMed][CrossRef]
123. Foà-Tomasi L, Avitabile E, Ke L, Campadelli-Fiume G. 1994. Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6. J Gen Virol 75:2719–2727. [PubMed][CrossRef]
124. Yoshikawa T, Black JB, Ihira M, Suzuki K, Suga S, Iida K, Saito Y, Asonuma K, Tanaka K, Asano Y. 2001. Comparison of specific serological assays for diagnosing human herpesvirus 6 infection after liver transplantation. Clin Diagn Lab Immunol 8:170–173. [PubMed][CrossRef]
125. Robert C, Aubin JT, Visse B, Fillet AM, Huraux JM, Agut H. 1996. Difference in permissiveness of human fibroblast cells to variants A and B of human herpesvirus-6. Res Virol 147:219–225. [PubMed][CrossRef]
126. Carrigan DR, Knox KK. 2000. Human herpesvirus 6: diagnosis of active infection. Am Clin Lab 19:12. [PubMed]
127. Lautenschlager I, Höckerstedt K, Linnavuori K, Taskinen E. 1998. Human herpesvirus-6 infection after liver transplantation. Clin Infect Dis 26:702–707. [PubMed][CrossRef]
128. Loginov R, Karlsson T, Höckerstedt K, Ablashi D, Lautenschlager I. 2010. Quantitative HHV-6B antigenemia test for the monitoring of transplant patients. Eur J Clin Microbiol Infect Dis 29:881–886. [PubMed][CrossRef]
129. Loginov R, Härmä M, Halme L, Höckerstedt K, Lautenschlager I. 2006. HHV-6 DNA in peripheral blood mononuclear cells after liver transplantation. J Clin Virol 37(Suppl 1) :S76–S81. [PubMed][CrossRef]
130. Siddon A, Lozovatsky L, Mohamed A, Hudnall SD. 2012. Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma. Br J Haematol 158:635–643. [PubMed][CrossRef]
131. Fernández-Ruiz M, Kumar D, Husain S, Lilly L, Renner E, Mazzulli T, Moussa G, Humar A. 2015. Utility of a monitoring strategy for human herpesviruses 6 and 7 viremia after liver transplantation: a randomized clinical trial. Transplantation 99:106–113. [PubMed][CrossRef]
132. Boutolleau D, Duros C, Bonnafous P, Caïola D, Karras A, Castro ND, Ouachée M, Narcy P, Gueudin M, Agut H, Gautheret-Dejean A. 2006. Identification of human herpesvirus 6 variants A and B by primer-specific real-time PCR may help to revisit their respective role in pathology. J Clin Virol 35:257–263. [PubMed][CrossRef]
133. Fernandez C, Boutolleau D, Manichanh C, Mangeney N, Agut H, Gautheret-Dejean A. 2002. Quantitation of HHV-7 genome by real-time polymerase chain reaction assay using MGB probe technology. J Virol Methods 106:11–16. [PubMed][CrossRef]
134. Flamand L, Gravel A, Boutolleau D, Alvarez-Lafuente R, Jacobson S, Malnati MS, Kohn D, Tang YW, Yoshikawa T, Ablashi D. 2008. Multicenter comparison of PCR assays for detection of human herpesvirus 6 DNA in serum. J Clin Microbiol 46:2700–2706. [PubMed][CrossRef]
135. Caserta MT, Hall CB, Schnabel K, Lofthus G, Marino A, Shelley L, Yoo C, Carnahan J, Anderson L, Wang H. 2010. Diagnostic assays for active infection with human herpesvirus 6 (HHV-6). J Clin Virol 48:55–57. [PubMed][CrossRef]
136. Pradeau K, Couty L, Szelag JC, Turlure P, Rolle F, Ferrat P, Bordessoule D, Le Meur Y, Denis F, Ranger-Rogez S. 2006. Multiplex real-time PCR assay for simultaneous quantitation of human cytomegalovirus and herpesvirus-6 in polymorphonuclear and mononuclear cells of transplant recipients. J Virol Methods 132:77–84. [PubMed][CrossRef]
137. Engelmann I, Petzold DR, Kosinska A, Hepkema BG, Schulz TF, Heim A. 2008. Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens. J Med Virol 80:467–477. [PubMed][CrossRef]
138. Andre-Garnier E, Robillard N, Costa-Mattioli M, Besse B, Billaudel S, Imbert-Marcille BM. 2003. A one-step RT-PCR and a flow cytometry method as two specific tools for direct evaluation of human herpesvirus-6 replication. J Virol Methods 108:213–222. [CrossRef]
139. Pradeau K, Bordessoule D, Szelag JC, Rolle F, Ferrat P, Le Meur Y, Turlure P, Denis F, Ranger-Rogez S. 2006. A reverse transcription-nested PCR assay for HHV-6 mRNA early transcript detection after transplantation. J Virol Methods 134:41–47. [PubMed][CrossRef]
140. Ihira M, Enomoto Y, Kawamura Y, Nakai H, Sugata K, Asano Y, Tsuzuki M, Emi N, Goto T, Miyamura K, Matsumoto K, Kato K, Takahashi Y, Kojima S, Yoshikawa T. 2012. Development of quantitative RT-PCR assays for detection of three classes of HHV-6B gene transcripts. J Med Virol 84:1388–1395. [PubMed][CrossRef]
141. Menegazzi P, Galvan M, Rotola A, Ravaioli T, Gonelli A, Cassai E, Di Luca D. 1999. Temporal mapping of transcripts in human herpesvirus-7. J Gen Virol 80:2705–2712. [PubMed][CrossRef]
142. Isegawa Y, Matsumoto C, Nishinaka K, Nakano K, Tanaka T, Sugimoto N, Ohshima A. 2010. PCR with quenching probes enables the rapid detection and identification of ganciclovir-resistance-causing U69 gene mutations in human herpesvirus 6. Mol Cell Probes 24:167–177. [PubMed][CrossRef]
143. Leibovitch EC, Brunetto GS, Caruso B, Fenton K, Ohayon J, Reich DS, Jacobson S. 2014. Coinfection of human herpesviruses 6A (HHV-6A) and HHV-6B as demonstrated by novel digital droplet PCR assay. PLoS One 9:e92328. doi.10.1371/journal.pone.0092328 [CrossRef]
144. Sedlak RH, Cook L, Huang ML, Magaret A, Zerr DM, Boeckh M, Jerome KR. 2014. Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR. Clin Chem 60:765–772. [PubMed][CrossRef]
145. Tuddenham L, Jung JS, Chane-Woon-Ming B, Dölken L, Pfeffer S. 2012. Small RNA deep sequencing identifies microRNAs and other small noncoding RNAs from human herpesvirus 6B. J Virol 86:1638–1649. [PubMed][CrossRef]
146. Ablashi D, Agut H, Alvarez-Lafuente R, Clark DA, Dewhurst S, Diluca D, Flamand L, Frenkel N, Gallo R, Gompels UA, Höllsberg P, Jacobson S, Luppi M, Lusso P, Malnati M, Medveczky P, Mori Y, Pellett PE, Pritchett JC, Yamanishi K, Yoshikawa T. 2013. Classification of HHV-6A and HHV-6B as distinct viruses. Arch Virol 159:863–870. [PubMed][CrossRef]
147. Reddy S, Manna P. 2005. Quantitative detection and differentiation of human herpesvirus 6 subtypes in bone marrow transplant patients by using a single real-time polymerase chain reaction assay. Biol Blood Marrow Transplant 11:530–541. [PubMed][CrossRef]
148. Zerr DM. 2006. Human herpesvirus 6: a clinical update. Herpes 13:20–24. [PubMed]
149. Suga S, Yoshikawa T, Kajita Y, Ozaki T, Asano Y. 1998. Prospective study of persistence and excretion of human herpesvirus-6 in patients with exanthem subitum and their parents. Pediatrics 102:900–904. [PubMed][CrossRef]
150. Caserta MT, Hall CB, Schnabel K, Long CE, D’Heron N. 1998. Primary human herpesvirus 7 infection: a comparison of human herpesvirus 7 and human herpesvirus 6 infections in children. J Pediatr 133:386–389. [CrossRef]
151. Géraudie B, Charrier M, Bonnafous P, Heurté D, Desmonet M, Bartoletti MA, Penasse C, Agut H, Gautheret-Dejean A. 2012. Quantitation of human herpesvirus-6A, -6B and -7 DNAs in whole blood, mononuclear and polymorphonuclear cell fractions from healthy blood donors. J Clin Virol 53:151–155. [PubMed][CrossRef]
152. Strenger V, Caselli E, Lautenschlager I, Schwinger W, Aberle SW, Loginov R, Gentili V, Nacheva E, DiLuca D, Urban C. 2014. Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6). Clin Microbiol Infect 20:1027–1032. [PubMed][CrossRef]
153. Hill JA, Sedlak RH, Jerome KR. 2014. Past, present, and future perspectives on the diagnosis of Roseolovirus infections. Curr Opin Virol 9C:84–90. [PubMed][CrossRef]
154. Achour A, Boutolleau D, Gautheret-Dejean A, Agut H. 2006. Is human herpesvirus-6 DNA in plasma the right marker for active infection? J Infect Dis 194:1795–1796; author reply 1796–1797. [PubMed]
155. Achour A, Boutolleau D, Slim A, Agut H, Gautheret-Dejean A. 2007. Human herpesvirus-6 (HHV-6) DNA in plasma reflects the presence of infected blood cells rather than circulating viral particles. J Clin Virol 38:280–285. [PubMed][CrossRef]
156. Ljungman P, Wang FZ, Clark DA, Emery VC, Remberger M, Ringdén O, Linde A. 2000. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol 111:774–781. [PubMed]
157. Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, Dhedin N, Vernant JP, Agut H. 2002. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Methods 100:27–35. [PubMed][CrossRef]
158. Ward KN, Leong HN, Nacheva EP, Howard J, Atkinson CE, Davies NW, Griffiths PD, Clark DA. 2006. Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J Clin Microbiol 44:1571–1574. [PubMed][CrossRef]
159. Gautheret-Dejean A, Henquell C, Mousnier F, Boutolleau D, Bonnafous P, Dhédin N, Settegrana C, Agut H. 2009. Different expression of human herpesvirus-6 (HHV-6) load in whole blood may have a significant impact on the diagnosis of active infection. J Clin Virol 46:33–36. [PubMed][CrossRef]
160. Boutolleau D, Bonduelle O, Sabard A, Devers L, Agut H, Gautheret-Dejean A; French ATL Study Group. 2005. Detection of human herpesvirus 7 DNA in peripheral blood reflects mainly CD4+ cell count in patients infected with HIV. J Med Virol 76:223–228. [PubMed][CrossRef]
161. Ogata M. 2009. Human herpesvirus 6 in hematological malignancies. J Clin Exp Hematop 49:57–67. [PubMed][CrossRef]
162. Yao K, Honarmand S, Espinosa A, Akhyani N, Glaser C, Jacobson S. 2009. Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol 65:257–267. [PubMed][CrossRef]
163. Kawamura Y, Sugata K, Ihira M, Mihara T, Mutoh T, Asano Y, Yoshikawa T. 2011. Different characteristics of human herpesvirus 6 encephalitis between primary infection and viral reactivation. J Clin Virol 51:12–19. [PubMed][CrossRef]
164. Ward KN, Leong HN, Thiruchelvam AD, Atkinson CE, Clark DA. 2007. Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis. J Clin Microbiol 45:1298–1304. [PubMed][CrossRef]
165. Alenda R, Alvarez-Lafuente R, Costa-Frossard L, Arroyo R, Mirete S, Alvarez-Cermeño JC, Villar LM. 2014. Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis. Eur J Neurol 21:1096–1101. [PubMed][CrossRef]
166. Hubacek P, Maalouf J, Zajickova M, Kouba M, Cinek O, Hyncicova K, Fales I, Cetkovsky P. 2007. Failure of multiple antivirals to affect high HHV-6 DNAaemia resulting from viral chromosomal integration in case of severe aplastic anaemia. Haematologica 92:e98–e100. [PubMed][CrossRef]
167. Daibata M, Taguchi T, Nemoto Y, Taguchi H, Miyoshi I. 1999. Inheritance of chromosomally integrated human herpesvirus 6 DNA. Blood 94:1545–1549. [PubMed]
168. Hubacek P, Virgili A, Ward KN, Pohlreich D, Keslova P, Goldova B, Markova M, Zajac M, Cinek O, Nacheva EP, Sedlacek P, Cetkovsky P. 2009. HHV-6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV-6 and fatal CMV pneumonitis. Br J Haematol 145:394–398. [PubMed][CrossRef]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015
2016-06-17
2021-04-21

Abstract:

Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/4/3/DMIH2-0007-2015.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015&mimeType=html&fmt=ahah

Figures

Human Herpesviruses 6A, 6B, and 7
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-1,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-1,properties={foaf_givenname=Henri, foaf_name=Henri Agut, foaf_surname=Agut, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff3],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff2],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-2,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-2,properties={foaf_givenname=Pascale, foaf_name=Pascale Bonnafous, foaf_surname=Bonnafous, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff5],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff4]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-3,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-3,properties={foaf_givenname=Agnès, foaf_name=Agnès Gautheret-Dejean, foaf_surname=Gautheret-Dejean, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff9],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff7],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff8],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff6]]}]]
Citation: Agut H, Bonnafous P, Gautheret-Dejean A. 2016. Human herpesviruses 6a, 6b, and 7. microbiolspec 4(3): doi:10.1128/microbiolspec.DMIH2-0007-2015
/content/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015.fig1
FIGURE 1
Proposal of algorithm for the diagnosis and therapy monitoring of HHV-6-associated disease in an immunocompromised patient. It must be recalled that some of the virological tests mentioned in this algorithm are not widely available in medical centers and that the predictive value of positive results for the diagnosis of infection or disease is not formally established for many of the indicated sample types.
microbiolspec/4/3/DMIH2-0007-2015-fig1_thmb.gif
microbiolspec/4/3/DMIH2-0007-2015-fig1.gif
Image of FIGURE 1

Click to view

FIGURE 1

Proposal of algorithm for the diagnosis and therapy monitoring of HHV-6-associated disease in an immunocompromised patient. It must be recalled that some of the virological tests mentioned in this algorithm are not widely available in medical centers and that the predictive value of positive results for the diagnosis of infection or disease is not formally established for many of the indicated sample types.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Human Herpesviruses 6A, 6B, and 7
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-1,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-1,properties={foaf_givenname=Henri, foaf_name=Henri Agut, foaf_surname=Agut, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff3],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff2],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-2,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-2,properties={foaf_givenname=Pascale, foaf_name=Pascale Bonnafous, foaf_surname=Bonnafous, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff5],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff4]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-3,webId=/content/author/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-3,properties={foaf_givenname=Agnès, foaf_name=Agnès Gautheret-Dejean, foaf_surname=Gautheret-Dejean, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff9],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff7],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff8],com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015-aff6]]}]]
Citation: Agut H, Bonnafous P, Gautheret-Dejean A. 2016. Human herpesviruses 6a, 6b, and 7. microbiolspec 4(3): doi:10.1128/microbiolspec.DMIH2-0007-2015
/content/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015.T1
TABLE 1
Clinical syndromes associated with HHV-6 infections
Generic image for table

Click to view

TABLE 1

Clinical syndromes associated with HHV-6 infections

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015
/content/microbiolspec/10.1128/microbiolspec.DMIH2-0007-2015.T2
TABLE 2
Diagnostic approaches for HHV-6 and HHV-7 infections
Generic image for table

Click to view

TABLE 2

Diagnostic approaches for HHV-6 and HHV-7 infections

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0007-2015

Supplemental Material

No supplementary material available for this content.

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error