LYMPHOPROLIFERATIVE SYNDROMES ASSOCIATED WITH HUMAN HERPESVIRUS-6A AND HUMAN HERPESVIRUS-6B

Main Article Content

Eva Eliassen
Gerhard R Krueger
Mario Luppi
Dharam Ablashi

Keywords

Human herpesvirus, HHV-6A, HHV-6B, Lymphoproliferative Disease.

Abstract

Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), and nodular sclerosis Hodgkin’s lymphoma. Herein, we discuss the conditions associated with the lymphoproliferative capacity of HHV-6, as well as the potential mechanisms behind them. Continued exploration on this topic may add to our understanding of the interactions between HHV-6 and the immune system and may open the doors to more accurate diagnosis and treatment of certain lymphoproliferative disorders. 

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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. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986;234(4776):596-601.

[2] Salahuddin SZ, Kelley AS, Krueger GR, Josephs SF, Gupta S, Ablashi DV. Human herpes virus-6 (HHV-6) in diseases. Clin Diagn Virol. 1993;1(2):81-100.

[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. Classification of HHV-6A and HHV-6B as distinct viruses. Arch Virol. 2014;159(5):863-70.

[4] Lusso P, Markham PD, Tschachler E, di Marzo Veronese F, Salahuddin SZ, Ablashi DV, Pahwa S, Krohn K, Gallo RC. In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). J Exp Med. 1988;167(5):1659-70.

[5] Ablashi DV, Salahuddin SZ, Josephs SF, Imam F, Lusso P, Gallo RC, Hung C, Lemp J, Markham PD. HBLV (or HHV-6) in human cell lines. Nature. 1987;329(6136):207.

[6] Biberfeld P, Kramarsky B, Salahuddin SZ, Gallo RC. Ultrastructural characterization of a new human B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease. J Natl Cancer Inst. 1987;79(5):933-41.

[7] Ablashi DV, Balachandran N, Josephs SF, Hung CL, Krueger GR, Kramarsky B, Salahuddin SZ, Gallo RC. Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates. Virology. 1991;184(2):545-52.

[8] Eizuru Y, Minematsu T, Minamishima Y, Kikuchi M, Yamanishi K, Takahashi M, Kurata T, Borisch Chappuis B, Ellinger K, Neipel F, Kirchner T, Kujath P, Fleckenstein B, Müller-Hermelink HK. Human herpesvirus 6 in lymph nodes. Lancet. 1989; 333(8628):40-1.

[9] Dolcetti R, Di Luca D, Mirandola P, De Vita S, De Re V, Carbone A, Tirelli U, Cassai E, Boiocchi M. Frequent detection of human herpesvirus 6 DNA in HIV-associated lymphadenopathy. Lancet. 1994;344(8921):543.

[10] Bertram G, Dreiner N, Krueger GR, Ramon A, Ablashi DV, Salahuddin SZ, Balachandram N. Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis. In Vivo. 1991;5(3):271-9.

[11] Krueger GR, Manak M, Bourgeois N, Ablashi DV, Salahuddin SZ, Josephs SS, Buchbinder A, Gallo RC, Berthold F, Tesch H. Persistent active herpes virus infection associated with atypical polyclonal lymphoproliferation (APL) and malignant lymphoma. Anticancer Res. 1989;9(6):1457-76.

[12] Chen T, Hudnall SD. Anatomical mapping of human herpesvirus reservoirs of infection. Mod Pathol. 2006;19(5):726-37.

[13] Di Luca D, Dolcetti R, Mirandola P, De Re V, Secchiero P, Carbone A, Boiocchi M, Cassai E. Human herpesvirus 6: a survey of presence and variant distribution in normal peripheral lymphocytes and lymphoproliferative disorders. J Infect Dis. 1994;170(1):211-5.

[14] Dolcetti R, Di Luca D, Carbone A, Mirandola P, De Vita S, Vaccher E, Sighinolfi L, Gloghini A, Tirelli U, Cassai E, Boiocchi M. Human herpesvirus 6 in human immunodeficiency virus-infected individuals: association with early histologic phases of lymphadenopathy syndrome but not with malignant lymphoproliferative disorders. J Med Virol. 1996;48(4):344-53.

[15] Fillet AM, Raphael M, Visse B, Audouin J, Poirel L, Agut H. Controlled study of human herpesvirus 6 detection in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma. The French Study Group for HIV-Associated Tumors. J Med Virol. 1995;45(1):106-12.

[16] Lusso P, Malnati MS, Garzino-Demo A, Crowley RW, Long EO, Gallo RC. Infection of natural killer cells by human herpesvirus 6. Nature. 1993;362(6419):458-62.

[17] Kondo K, Kondo T, Okuno T, Takahashi M, Yamanishi K. Latent human herpesvirus 6 infection of human monocytes/macrophages. J Gen Virol. 1991;72 (Pt 6):1401-8.

[18] Kondo K, Kondo T, Shimada K, Amo K, Miyagawa H, Yamanishi K. Strong interaction between human herpesvirus 6 and peripheral blood monocytes/macrophages during acute infection. J Med Virol. 2002;67(3):364-9.

[19] Hirata Y, Kondo K, Yamanishi K. Human herpesvirus 6 downregulates major histocompatibility complex class I in dendritic cells. J Med Virol. 2001;65(3):576-83.

[20] Ablashi DV, Josephs SF, Buchbinder A, Hellman K, Nakamura S, Llana T, Lusso P, Kaplan M, Dahlberg J, Memon S, Imam F, Ablashi KL, Markham PD, Kramarsky B, Krueger GRF, Biberfeld P, Wong-Staal F, Salahuddin SZ, Gallo RC. Human B-lymphotropic virus (human herpesvirus-6). J Virol Methods. 1988; 21(1-4):29-48.

[21] Krueger GRF, Schneider B. Pathologic Features of HHV-6 Disease. In: Krueger GRF, Ablashi D, eds. Perspectives in Medical Virology. Volume 12, Elsevier. 2006; 133-48.

[22] Sandhoff T, Kleim JP, Schneweis KE. Latent human herpesvirus-6 DNA is sparsely distributed in peripheral blood lymphocytes of healthy adults and patients with lymphocytic disorders. Med Microbiol Immunol. 1991;180(3):127-34.

[23] Yakushijin Y, Yasukawa M, Kobayashi Y. T-cell immune response to human herpesvirus-6 in healthy adults. Microbiol Immunol. 1991;35(8):655-60.

[24] Nastke MD, Becerra A, Yin L, Dominguez-Amorocho O, Gibson L, Stern LJ, Calvo-Calle JM. Human CD4+ T cell response to human herpesvirus 6. J Virol. 2012;86(9):4776-92.

[25] Martin LK, Schub A, Dillinger S, Moosmann A. Specific CD8? T cells recognize human herpesvirus 6B. Eur J Immunol. 2012;42(11):2901-12.

[26] Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet. 1988;1(8594):1065-7.

[27] Knox KK, Carrigan DR. In vitro suppression of bone marrow progenitor cell differentiation by human herpesvirus 6 infection. J Infect Dis. 1992;165(5):925-9.

[28] Carrigan DR, Knox KK. Bone marrow suppression by human herpesvirus-6: comparison of the A and B variants of the virus. Blood. 1995;86(2):835-6.

[29] Horvat RT, Parmely MJ, Chandran B. Human herpesvirus 6 inhibits the proliferative responses of human peripheral blood mononuclear cells. J Infect Dis. 1993;167(6):1274-80.

[30] Flamand L, Gosselin J, Stefanescu I, Ablashi D, Menezes J. Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation. Blood. 1995;85(5):1263-71. Erratum in: Blood 1995;86(1):418.

[31] Yoshikawa T, Ihira M, Asano Y, Tomitaka A, Suzuki K, Matsunaga K, Kato Y, Hiramitsu S, Nagai T, Tanaka N, Kimura H, Nishiyama Y. Fatal adult case of severe lymphocytopenia associated with reactivation of human herpesvirus 6. J Med Virol. 2002;66(1):82-5.

[32] Knox KK, Pietryga D, Harrington DJ, Franciosi R, Carrigan DR. Progressive immunodeficiency and fatal pneumonitis associated with human herpesvirus 6 infection in an infant. Clin Infect Dis. 1995;20(2):406-13.

[33] Comar M, D'Agaro P, Horejsh D, Galvan M, Fiorentini S, Andolina M, Caruso A, Di Luca D, Campello C. Long-lasting CD3+ T-cell deficiency after cord blood stem cell transplantation in a human herpesvirus 6-infected child. J Clin Microbiol. 2005;43(4):2002-3.

[34] Imbert-Marcille BM, Tang XW, Lepelletier D, Besse B, Moreau P, Billaudel S, Milpied N. Human herpesvirus 6 infection after autologous or allogeneic stem cell transplantation: a single-center prospective longitudinal study of 92 patients. Clin Infect Dis. 2000;31(4):881-6.

[35] Rosenfeld CS, Rybka WB, Weinbaum D, Carrigan DR, Knox KK, Andrews DF, Shadduck RK. Late graft failure due to dual bone marrow infection with variants A and B of human herpesvirus-6. Exp Hematol. 1995;23(7):626-9.

[36] Admiraal R, de Koning CCH, Lindemans CA, Bierings MB, Wensing AMJ, Versluys AB, Wolfs TFW, Nierkens S, Boelens JJ. Viral reactivations and associated outcomes in the context of immune reconstitution after pediatric hematopoietic cell transplantation. J Allergy Clin Immunol. 2017;140(6):1643-1650.e9. Epub 2017 Apr 7.

[37] Greco R, Crucitti L, Noviello M, Racca S, Mannina D, Forcina A, Lorentino F, Valtolina V, Rolla S, Dvir R, Morelli M, Giglio F, Barbanti MC, Lupo Stanghellini MT, Oltolini C, Vago L, Scarpellini P, Assanelli A, Carrabba MG, Marktel S, Bernardi M, Corti C, Clementi M, Peccatori J, Bonini C, Ciceri F. Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune Recovery and Outcome. Biol Blood Marrow Transplant. 2016;22(12):2250-5.

[38] Quintela A, Escuret V, Roux S, Bonnafous P, Gilis L, Barraco F, Labussière-Wallet H, Duscastelle-Leprêtre S, Nicolini FE, Thomas X, Chidiac C, Ferry T, Frobert E, Morisset S, Poitevin-Later F, Monneret G, Michallet M, Ader F; Lyon HEMINF Study Group. HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns. J Infect. 2016;72(2):214-22.

[39] Wang FZ, Linde A, Dahl H, Ljungman P. Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation. Bone Marrow Transplant. 1999;24(11):1201-6.

[40] Illiaquer M, Imbert-Marcille BM, Guillaume T, Planche L, Rimbert M, Bressollette-Bodin C, Le Bourgeois A, Peterlin P, Garnier A, Le Houerou C, Moreau P, Mohty M, Chevallier P. Impact of stem cell graft on early viral infections and immune reconstitution after allogeneic transplantation in adults. J Clin Virol. 2017;93:30-6.

[41] Smith A, Santoro F, Di Lullo G, Dagna L, Verani A, Lusso P. Selective suppression of IL-12 production by human herpesvirus 6. Blood. 2003;102(8):2877-84.

[42] Smith AP, Paolucci C, Di Lullo G, Burastero SE, Santoro F, Lusso P. Viral replication-independent blockade of dendritic cell maturation and interleukin-12 production by human herpesvirus 6. J Virol. 2005;79(5):2807-13.

[43] Flamand L, Gosselin J, D'Addario M, Hiscott J, Ablashi DV, Gallo RC, Menezes J. Human herpesvirus 6 induces interleukin-1 beta and tumor necrosis factor alpha, but not interleukin-6, in peripheral blood mononuclear cell cultures. J Virol. 1991;65(9):5105-10.

[44] Arena A, Liberto MC, Iannello D, Capozza AB, Focà A. Altered cytokine production after human herpes virus type 6 infection. New Microbiol. 1999;22(4):293-300.

[45] Kikuta H, Nakane A, Lu H, Taguchi Y, Minagawa T, Matsumoto S. Interferon induction by human herpesvirus 6 in human mononuclear cells. J Infect Dis. 1990;162(1):35-8.

[46] Chi J, Gu B, Zhang C, Peng G, Zhou F, Chen Y, Zhang G, Guo Y, Guo D, Qin J, Wang J, Li L, Wang F, Liu G, Xie F, Feng D, Zhou H, Huang X, Lu S, Liu Y, Hu W, Yao K. Human herpesvirus 6 latent infection in patients with glioma. J Infect Dis. 2012;206(9):1394-8.

[47] Yoshikawa T, Asano Y, Akimoto S, Ozaki T, Iwasaki T, Kurata T, Goshima F, Nishiyama Y. Latent infection of human herpesvirus 6 in astrocytoma cell line and alteration of cytokine synthesis. J Med Virol. 2002;66(4):497-505.

[48] Meeuwsen S, Persoon-Deen C, Bsibsi M, Bajramovic JJ, Ravid R, De Bolle L, van Noort JM. Modulation of the cytokine network in human adult astrocytes by human herpesvirus-6A. J Neuroimmunol. 2005;164(1-2):37-47.

[49] Clark DJ, Catusse J, Stacey A, Borrow P, Gompels UA. Activation of CCR2+ human proinflammatory monocytes by human herpesvirus-6B chemokine N-terminal peptide. J Gen Virol. 2013;94(Pt 7):1624-35.

[50] Caselli E, Bortolotti D, Marci R, Rotola A, Gentili V, Soffritti I, D'Accolti M, Lo Monte G, Sicolo M, Barao I, Di Luca D, Rizzo R. HHV-6A Infection of Endometrial Epithelial Cells Induces Increased Endometrial NK Cell-Mediated Cytotoxicity. Front Microbiol. 2017;8:2525.

[51] Catusse J, Clark DJ, Gompels UA. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway. J Inflamm (Lond). 2009;6:22.

[52] Catusse J, Spinks J, Mattick C, Dyer A, Laing K, Fitzsimons C, Smit MJ, Gompels UA. Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes. Eur J Immunol. 2008;38(3):763-77.

[53] Nagasaka M, Morioka I, Kawabata A, Yamagishi Y, Iwatani S, Taniguchi-Ikeda M, Ishida A, Iijima K, Mori Y. Comprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infection. J Infect Chemother. 2016;22(9):593-8.

[54] Krueger GRF, Schonnebeck M, Braun M. Enhanced cell membrane receptor expression following infection with human herpesvirus-6. FASEB J. 1990;4:A343.

[55] Schonnebeck M, Krueger GRF, Braun M, Fischer M, Koch B, Ablashi DV, Balachandran N. Human herpesvirus-6 infection may predispose to superinfection by other viruses. In Vivo. 1991;5: 255-64.

[56] Santoro F, Kennedy PE, Locatelli G, Malnati MS, Berger EA, Lusso P. CD46 is a cellular receptor for human herpesvirus 6. Cell. 1999;99(7):817-27.

[57] Glosson NL, Hudson AW. Human herpesvirus-6A and -6B encode viral immunoevasins that downregulate class I MHC molecules. Virology. 2007;365(1):125-35.

[58] Grivel JC, Santoro F, Chen S, Fagá G, Malnati MS, Ito Y, Margolis L, Lusso P. Pathogenic effects of human herpesvirus 6 in human lymphoid tissue ex vivo. J Virol. 2003;77(15):8280-9.

[59] Sullivan BM, Coscoy L. Downregulation of the T-cell receptor complex and impairment of T-cell activation by human herpesvirus 6 u24 protein. J Virol. 2008;82(2):602-8.

[60] Lusso P, Malnati M, De Maria A, Balotta C, DeRocco SE, Markham PD, Gallo RC. Productive infection of CD4+ and CD8+ mature human T cell populations and clones by human herpesvirus 6. Transcriptional down-regulation of CD3. J Immunol. 1991;147(2):685-91.

[61] Lusso P, Garzino-Demo A, Crowley RW, Malnati MS. Infection of gamma/delta T lymphocytes by human herpesvirus 6: transcriptional induction of CD4 and susceptibility to HIV infection. J Exp Med. 1995;181(4):1303-10.

[62] Furukawa M, Yasukawa M, Yakushijin Y, Fujita S. Distinct effects of human herpesvirus 6 and human herpesvirus 7 on surface molecule expression and function of CD4+ T cells. J Immunol. 1994;152(12):5768-75.

[63] Zheng X, Li S, Zang Z, Hu J, An J, Pei X, Zhu F, Zhang W, Yang H. Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas. Mol Cell Endocrinol. 2016;426:22-32.

[64] Reynaud JM, Jégou JF, Welsch JC, Horvat B. Human herpesvirus 6A infection in CD46 transgenic mice: viral persistence in the brain and increased production of proinflammatory chemokines via Toll-like receptor 9. J Virol. 2014;88(10):5421-36.

[65] Nordström I, Eriksson K. HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. PLoS One. 2012;7(6):e38683. Epub 2012 Jun 6.

[66] Chi J, Wang F, Li L, Feng D, Qin J, Xie F, Zhou F, Chen Y, Wang J, Yao K. The role of MAPK in CD4(+) T cells toll-like receptor 9-mediated signaling following HHV-6 infection. Virology. 2012;422(1):92-8.

[67] Murakami Y, Tanimoto K, Fujiwara H, An J, Suemori K, Ochi T, Hasegawa H, Yasukawa M. Human herpesvirus 6 infection impairs Toll-like receptor signaling. Virol J. 2010;7:91.

[68] Krueger GRF, Sander C. What’s New in Human Herpesvirus-6? Clinical Immunopathology of the HHV-6 Infection. Pathol Res Pract. 1989 Dec;185(6):915-29.

[69] Mullins TB, Krishnamurthy K. Roseola Infantum (Exanthema Subitum, Sixth Disease). In: StatPearls [Internet]. Treasure Island, StatPearls Publishing. 2018.

[70] Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, Knott A, Dewhurst S, Insel RA, Epstein LG. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994;331(7):432-8.

[71] Asano Y, Yoshikawa T, Suga S, Kobayashi I, Nakashima T, Yazaki T, Kajita Y, Ozaki T. Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum). Pediatrics. 1994;93(1):104-8.

[72] de Freitas RB, Linhares AC, Oliveira CS, Gusmão RH, Linhares MI. Association of human herpesvirus 6 infection with exanthem subitum in Belem, Brazil. Rev Inst Med Trop Sao Paulo. 1995;37(6):489-92.

[73] Balachandra K, Bowonkiratikachorn P, Poovijit B, Thattiyaphong A, Jayavasu C, Wasi C, Takahashi M, Yamanishi K. Human herpesvirus 6 (HHV-6) infection and exanthem subitum in Thailand. Acta Paediatr Jpn. 1991;33(4):434-9.

[74] Hashimoto H, Maruyama H, Fujimoto K, Sakakura T, Seishu S, Okuda N. Hematologic findings associated with thrombocytopenia during the acute phase of exanthem subitum confirmed by primary human herpesvirus-6 infection. J Pediatr Hematol Oncol. 2002;24(3):211-4.

[75] Yoshikawa T, Suzuki K, Umemura K, Akimoto S, Miyake F, Usui C, Fujita A, Suga S, Asano Y. Atypical clinical features of a human herpesvirus-6 infection in a neonate. J Med Virol. 2004;74(3):463-6.

[76] Kanegane C, Katayama K, Kyoutani S, Kanegane H, Shintani N, Miyawaki T, Taniguchi N. Mononucleosis-like illness in an infant associated with human herpesvirus 6 infection. Acta Paediatr Jpn. 1995;37(2):227-9.

[77] Hoang MP, Ross KF, Dawson DB, Scheuermann RH, Rogers BB. Human herpesvirus-6 and sudden death in infancy: report of a case and review of the literature. J Forensic Sci. 1999;44(2):432-7.

[78] Lorenzana A, Lyons H, Sawaf H, Higgins M, Carrigan D, Emanuel PD. Human herpesvirus 6 infection mimicking juvenile myelomonocytic leukemia in an infant. J Pediatr Hematol Oncol. 2002;24(2):136-41.

[79] Krueger GRF, Ablashi DV, Whitman J, Luka J, Rojo J. Clinical pathology and reactivation of human lymphotropic herpesviruses. Revista Med Hops Gen Mexico. 1998;61:226-40.

[80] Irving WL, Cunningham AL. Serological diagnosis of infection with human herpesvirus type 6. BMJ. 1990;300(6718):156-9.

[81] Borisch B, Ellinger K, Neipel F, Fleckenstein B, Kirchner T, Ott MM, Müller-Hermelink HK. Lymphadenitis and lymphoproliferative lesions associated with the human herpes virus-6 (HHV-6). Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(3):179-87.

[82] Niederman JC, Liu CR, Kaplan MH, Brown NA. Clinical and serological features of human herpesvirus-6 infection in three adults. Lancet. 1988;2(8615):817-9.

[83] Stettner-Gloning R, Jäger G, Gloning H, Pontz BF, Emmrich P. Lymphadenopathy in connection with human herpes virus type 6 (HHV-6) infection. Clin Investig. 1992;70(1):59-62.

[84] Asou H, Tasaka T, Said JW, Daibata M, Kamada N, Koeffler HP. Co-infection of HHV-6 and HHV-8 is rare in primary effusion lymphoma. Leuk Res. 2000;24(1):59-61.

[85] Luppi M, Barozzi P, Garber R, Maiorana A, Bonacorsi G, Artusi T, Trovato R, Marasca R, Torelli G. Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases. Am J Pathol. 1998;153(3):815-23.

[86] Sandhoff T, Kleim JP, Schneweis KE. Latent human herpesvirus-6 DNA is sparsely distributed in peripheral blood lymphocytes of healthy adults and patients with lymphocytic disorders. Med Microbiol Immunol. 1991;180(3):127-34.

[87] Freitas RB, Freitas MR, Linhares AC. Evidence of active herpesvirus 6 (variant-A) infection in patients with lymphadenopathy in Belém, Pará, Brazil. Rev Inst Med Trop Sao Paulo. 2003;45(5):283-8.

[88] Forghieri F, Luppi M, Barozzi P, Riva G, Morselli M, Bigliardi S, Quadrelli C, Vallerini D, Maccaferri M, Coluccio V, Paolini A, Colaci E, Bonacorsi G, Maiorana A, Tagliazucchi S, Rumpianesi F, Mattioli F, Presutti L, Gelmini R, Cermelli C, Rossi G, Comoli P, Marasca R, Narni F, Potenza L. Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation. Br J Haematol. 2016;172(4):561-72.

[89] Weiss LM, O'Malley D. Benign lymphadenopathies. Mod Pathol. 2013;26 Suppl 1:S88-96.

[90] Levine PH, Jahan N, Murari P, Manak M, Jaffe ES. Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). J Infect Dis. 1992;166(2):291-5.

[91] Scheel MM, Rady PL, Tyring SK, Pandya AG. Sinus histiocytosis with massive lymphadenopathy: presentation as giant granuloma annulare and detection of human herpesvirus 6. J Am Acad Dermatol. 1997;37(4):643-6.

[92] Arakaki N, Gallo G, Majluf R, Diez B, Arias E, Riudavets MA, Sevlever G. Extranodal rosai-dorfman disease presenting as a solitary mass with human herpesvirus 6 detection in a pediatric patient. Pediatr Dev Pathol. 2012;15(4):324-8.

[93] Ortonne N, Fillet AM, Kosuge H, Bagot M, Frances C, Wechsler J. Cutaneous Destombes-Rosai-Dorfman disease: absence of detection of HHV-6 and HHV-8 in skin. J Cutan Pathol. 2002;29(2):113-8.

[94] Hoffmann A, Kirn E, Kuerten A, Sander C, Krueger GR, Ablashi DV. Active human herpesvirus-6 (HHV-6) infection associated with Kikuchi-Fujimoto disease and systemic lupus erythematosus (SLE). In Vivo. 1991;5(3):265-9.

[95] Rodríguez JN, Aguayo DM, Elizalde J, Martino ML, Moreno MV, Lara C, Prados D. Kikuchi-Fujimoto disease associated with acute infection by herpesvirus 6. Sangre (Barc). 1996;41(5):387-90.

[96] Hollingsworth HC, Peiper SC, Weiss LM, Raffeld M, Jaffe ES. An investigation of the viral pathogenesis of Kikuchi-Fujimoto disease. Lack of evidence for Epstein-Barr virus or human herpesvirus type 6 as the causative agents. Arch Pathol Lab Med. 1994;118(2):134-40.

[97] Rosado FG, Tang YW, Hasserjian RP, McClain CM, Wang B, Mosse CA. Kikuchi-Fujimoto lymphadenitis: role of parvovirus B-19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8. Hum Pathol. 2013;44(2):255-9.

[98] Sumiyoshi Y, Kikuchi M, Ohshima K, Yoneda S, Kobari S, Takeshita M, Eizuru Y, Minamishima Y. Human herpesvirus-6 genomes in histiocytic necrotizing lymphadenitis (Kikuchi's disease) and other forms of lymphadenitis. Am J Clin Pathol. 1993;99(5):609-14.

[99] Usui Y, Rao NA, Takase H, Tsubota K, Umazume K, Diaz-Aguilar D, Kezuka T, Mochizuki M, Goto H, Sugita S. Comprehensive polymerase chain reaction assay for detection of pathogenic DNA in lymphoproliferative disorders of the ocular adnexa. Sci Rep. 2016;6:36621.

[100] Sugita S, Shimizu N, Kawaguchi T, Akao N, Morio T, Mochizuki M. Identification of human herpesvirus 6 in a patient with severe unilateral panuveitis. Arch Ophthalmol. 2007;125(10):1426-7.

[101] Sugita S, Shimizu N, Watanabe K, Ogawa M, Maruyama K, Usui N, Mochizuki M. Virological analysis in patients with human herpes virus 6-associated ocular inflammatory disorders. Invest Ophthalmol Vis Sci. 2012;53(8):4692-8.

[102] Bai Y, Wang Z, Sun K, Yao H. HHV-6-associated acute lymphadenitis in immunocompetent patients: a case report and review of literature. Int J Clin Exp Pathol. 2014;7(6):3413-7.

[103] Krueger GR, Ablashi DV, Salahuddin SZ, Josephs SF. Diagnosis and differential diagnosis of progressive lymphoproliferation and malignant lymphoma in persistent active herpesvirus infection. J Virol Methods. 1988;21(1-4):255-64.

[104] Karino T, Asaoka N, Sunagawa T, Ohba H, Yoneyama H, Kobashi Y, Okimoto J, Soejima R. A case with infectious mononucleosis-like syndrome caused by human herpes virus-6 infection. Kansenshogaku Zasshi. 2000;74(3):264-8.

[105] Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, Ritz J, Nadler LM, Komaroff AL. A chronic "postinfectious" fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990;10(6):335-44.

[106] Steeper TA, Horwitz CA, Ablashi DV, Salahuddin SZ, Saxinger C, Saltzman R, Schwartz B. The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus. Am J Clin Pathol. 1990;93(6):776-83.

[107] Naito T, Kudo N, Inui A, Matsumoto N, Takeda N, Isonuma H, Dambara T, Hayashida Y. Causes of infectious mononucleosis-like syndrome in adult patients. Intern Med. 2006;45(13):833-4.

[108] Horwitz CA, Krueger GRF, Steeper TA, Bertram G. HHV-6-induced mononucleosis-like illnesses. Perspectives in Medical Virology. 1992;4:159-74.

[109] Ramon A, Krueger GRF, Simoes P, Jockenhoevel F, Neumann R, Rojo J, Ablashi DV: Immunopathology of liver diseases. Revista Med Hosp Gen Mexico. 1998;61:241-61.

[110] Kirchesch H, Mertens T, Burkhardt U, Kruppenbacher JP, Höffken A, Eggers HJ. Seroconversion against human herpesvirus-6 (and other herpesviruses) and clinical illness. Lancet. 1988;2(8605):273-4.

[111] Sobue R, Miyazaki H, Okamoto M, Hirano M, Yoshikawa T, Suga S, Asano Y. Fulminant hepatitis in primary human herpesvirus-6 infection. N Engl J Med. 1991;324(18):1290.

[112] Krueger GR, Bertram G, Ramon A, Koch B, Ablashi DV, Brandt ME, Wang G, Buja LM. Dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis: data acquisition for computer modeling. In Vivo. 2001;15(5):373-80.

[113] Akashi K, Eizuru Y, Sumiyoshi Y, Minematsu T, Hara S, Harada M, Kikuchi M, Niho Y, Minamishima Y. Brief report: severe infectious mononucleosis-like syndrome and primary human herpesvirus 6 infection in an adult. N Engl J Med. 1993;329(3):168-71.

[114] Sumiyoshi Y, Akashi K, Kikuchi M. Detection of human herpes virus 6 (HHV 6) in the skin of a patient with primary HHV 6 infection and erythroderma. J Clin Pathol. 1994;47(8):762-3.

[115] Sumiyoshi Y, Kikuchi M, Ohshima K, Takeshita M, Eizuru Y, Minamishima Y. A case of human herpesvirus-6 lymphadenitis with infectious mononucleosis-like syndrome. Pathol Int. 1995;45(12):947-51.

[116] Tsaparas YF, Brigden ML, Mathias R, Thomas E, Raboud J, Doyle PW. Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag. Arch Pathol Lab Med. 2000;124(9):1324-30.

[117] Wang G, Krueger GR, Buja LM. Mathematical model to simulate the cellular dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis. J Med Virol. 2003;71(4):569-77.

[118] Krueger GR, Brandt ME, Wang G, Berthold F, Buja LM. A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma. Anticancer Res. 2002;22(4):2365-71.

[119] Hoang MP, Dawson DB, Rogers ZR, Scheuermann RH, Rogers BB. Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis. Hum Pathol. 1998;29(10):1074-7.

[120] Syr?cková Z, Starý J, Sedlácek P, Smísek P, Vavrinec J, Komrska V, Roubalová K, Vandasová J, Sintáková B, Housková J, Hassan M. Infection-associated hemophagocytic syndrome complicated by infectious lymphoproliferation: a case report. Pediatr Hematol Oncol. 1996;13(2):143-50.

[121] Tadokoro R, Okumura A, Nakazawa T, Hara S, Yamakawa Y, Kamata A, Kinoshita K, Obinata K, Shimizu T. Acute encephalopathy with biphasic seizures and late reduced diffusion associated with hemophagocytic syndrome. Brain Dev. 2010;32(6):477-81.

[122] Tanaka H, Nishimura T, Hakui M, Sugimoto H, Tanaka-Taya K, Yamanishi K. Human herpesvirus 6-associated hemophagocytic syndrome in a healthy adult. Emerg Infect Dis. 2002;8(1):87-8.

[123] Dharancy S, Crombe V, Copin MC, Boleslawski E, Bocket L, Declerck N, Canva V, Dewilde A, Mathurin P, Pruvot FR. Fatal hemophagocytic syndrome related to human herpesvirus-6 reinfection following liver transplantation: a case report. Transplant Proc. 2008;40(10):3791-3.

[124] Marabelle A, Bergeron C, Billaud G, Mekki Y, Girard S. Hemophagocytic syndrome revealing primary HHV-6 infection. J Pediatr. 2010;157(3):511.

[125] Takagi M, Unno A, Maruyama T, Kaneko K, Obinata K. Human herpesvirus-6 (HHV-6)-associated hemophagocytic syndrome. Pediatr Hematol Oncol. 1996;13(5):451-6.

[126] Chen RL, Lin KH, Lin DT, Su IJ, Huang LM, Lee PI, Hseih KH, Lin KS, Lee CY. Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis. Br J Haematol. 1995;89(2):282-90.

[127] Huang LM, Lee CY, Lin KH, Chuu WM, Lee PI, Chen RL, Chen JM, Lin DT. Human herpesvirus-6 associated with fatal haemophagocytic syndrome. Lancet. 1990;336(8706):60-1.

[128] Liu DL, Teng RJ, Ho MM, Hwang KC, Hwang LM. Human herpesvirus-6 associated hemophagocytic syndrome in beta-thalassemia: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1995;36(5):373-5.

[129] Randhawa PS, Jenkins FJ, Nalesnik MA, Martens J, Williams PA, Ries A, Pham S, Demetris AJ. Herpesvirus 6 variant A infection after heart transplantation with giant cell transformation in bile ductular and gastroduodenal epithelium. Am J Surg Pathol. 1997;21(7):847-53.

[130] Potenza L, Luppi M, Barozzi P, Rossi G, Cocchi S, Codeluppi M, Pecorari M, Masetti M, Di Benedetto F, Gennari W, Portolani M, Gerunda GE, Lazzarotto T, Landini MP, Schulz TF, Torelli G, Guaraldi G. HHV-6A in syncytial giant-cell hepatitis. N Engl J Med. 2008;359(6):593-602.

[131] Mori Y, Seya T, Huang HL, Akkapaiboon P, Dhepakson P, Yamanishi K. Human herpesvirus 6 variant A but not variant B induces fusion from without in a variety of human cells through a human herpesvirus 6 entry receptor, CD46. J Virol. 2002;76(13):6750-61.

[132] Pedersen SM, Oster B, Bundgaard B, Höllsberg P. Induction of cell-cell fusion from without by human herpesvirus 6B. J Virol. 2006;80(19):9916-20.

[133] Bastida-Ruiz D, Van Hoesen K, Cohen M. The Dark Side of Cell Fusion. Int J Mol Sci. 2016;17(5):638.

[134] Lautenschlager I, Härmä M, Höckerstedt K, Linnavuori K, Loginov R, Taskinen E. Human herpesvirus-6 infection is associated with adhesion molecule induction and lymphocyte infiltration in liver allografts. J Hepatol. 2002;37(5):648-54.

[135] Schmitt K, Deutsch J, Tulzer G, Meindi R, Aberle S. Autoimmune hepatitis and adrenal insufficiency in an infant with human herpesvirus-6 infection. Lancet. 1996;348(9032):966.

[136] Charnot-Katsikas A, Baewer D, Cook L, David MZ. Fulminant hepatic failure attributed to infection with human herpesvirus 6 (HHV-6) in an immunocompetent woman: A case report and review of the literature. J Clin Virol. 2016;75:27-32.

[137] Asano Y, Yoshikawa T, Suga S, Yazaki T, Kondo K, Yamanishi K. Fatal fulminant hepatitis in an infant with human herpesvirus-6 infection. Lancet. 1990;335(8693):862-3.

[138] Chang YL, Parker ME, Nuovo G, Miller JB. Human herpesvirus 6-related fulminant myocarditis and hepatitis in an immunocompetent adult with fatal outcome. Hum Pathol. 2009;40(5):740-5.

[139] Grima P, Chiavaroli R, Calabrese P, Tundo P, Grima P. Severe hepatitis with autoimmune features following a HHV-6: a case report. Cases J. 2008;1(1):110.

[140] Descamps V, Bouscarat F, Laglenne S, Aslangul E, Veber B, Descamps D, Saraux JL, Grange MJ, Grossin M, Navratil E, Crickx B, Belaich S. Human herpesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome. Br J Dermatol. 1997;137(4):605-8.

[141] Johnson S, Mathews S, Hudnall SD. Human herpesvirus 6 lymphadenitis in drug rash with eosinophilia and systemic symptoms syndrome: a lymphoma mimic. Histopathology. 2017;70(7):1166-70.

[142] Saraya T, Mikoshiba M, Kamiyama H, Yoshizumi M, Tsuchida S, Tsukagoshi H, Ishioka T, Terada M, Tanabe E, Tomioka C, Ishii H, Kimura H, Kozawa K, Shiohara T, Takizawa H, Goto H. Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome. J Clin Microbiol. 2013;51(6):1979-82.

[143] Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, Chosidow O, Guillot I, Paradis V, Joly P, Crickx B, Ranger-Rogez S, Descamps V. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure. Arch Dermatol. 2009;145(1):67-72.

[144] Fujino Y, Nakajima M, Inoue H, Kusuhara T, Yamada T. Human herpesvirus 6 encephalitis associated with hypersensitivity syndrome. Ann Neurol. 2002;51(6):771-4.

[145] Mennicke M, Zawodniak A, Keller M, Wilkens L, Yawalkar N, Stickel F, Keogh A, Inderbitzin D, Candinas D, Pichler WJ. Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplantation. Am J Transplant. 2009;9(9):2197-202.

[146] Miyashita K, Shobatake C, Miyagawa F, Kobayashi N, Onmori R, Yonekawa S, Tanabe K, Kawate K, Morita K, Asada H. Involvement of Human Herpesvirus 6 Infection in Renal Dysfunction Associated with DIHS/DRESS. Acta Derm Venereol. 2016;96(1):114-5.

[147] Hagiya H, Iwamuro M, Tanaka T, Hasegawa K, Hanayama Y, Kimura M, Otsuka F. Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS). Intern Med. 2016;55(13):1769-74.

[148] Mine S, Suzuki K, Sato Y, Fukumoto H, Kataoka M, Inoue N, Ohbayashi C, Hasegawa H, Sata T, Fukayama M, Katano H. Evidence for human herpesvirus-6B infection of regulatory T-cells in acute systemic lymphadenitis in an immunocompetent adult with the drug reaction with eosinophilia and systemic symptoms syndrome: a case report. J Clin Virol. 2014;61(3):448-52.

[149] Descamps V, Ranger-Rogez S. DRESS syndrome. Joint Bone Spine. 2014;81(1):15-21.

[150] Nakazato T, Suzuki K, Mihara A, Sanada Y, Aisa Y, Kakimoto T. ATL-like marked atypical lymphocytosis associated with drug-induced hypersensitivity syndrome and human herpesvirus-6 reactivation. Int J Hematol. 2009;90(5):648-50.

[151] Tohyama M, Hashimoto K, Yasukawa M, Kimura H, Horikawa T, Nakajima K, Urano Y, Matsumoto K, Iijima M, Shear NH. Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol. 2007;157(5):934-40.

[152] Maric I, Bryant R, Abu-Asab M, Cohen JI, Vivero A, Jaffe ES, Raffeld M, Tsokos M, Banks PM, Pittaluga S. Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults. Mod Pathol. 2004;17(11):1427-33.

[153] Takahashi R, Kano Y, Yamazaki Y, Kimishima M, Mizukawa Y, Shiohara T. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. J Immunol. 2009;182(12):8071-9.

[154] Wang F, Chi J, Peng G, Zhou F, Wang J, Li L, Feng D, Xie F, Gu B, Qin J, Chen Y, Yao K. Development of virus-specific CD4+ and CD8+ regulatory T cells induced by human herpesvirus 6 infection. J Virol. 2014;88(2):1011-24.

[155] Wang F, Yao K, Yin QZ, Zhou F, Ding CL, Peng GY, Xu J, Chen Y, Feng DJ, Ma CL, Xu WR. Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals. Microbiol Immunol. 2006;50(10):787-803.

[156] Fazakas A, Csire M, Berencsi G, Szepesi A, Matolcsy A, Jakab L, Karádi I, Várkonyi J. Multicentric plasmocytic Castleman's disease with polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes syndrome and coexistent human herpes virus-6 infection--a possible relationship. Leuk Lymphoma. 2009;50(10):1661-5.

[157] Ohyashiki JH, Abe K, Ojima T, Wang P, Zhou CF, Suzuki A, Ohyashiki K, Yamamoto K. Quantification of human herpesvirus 6 in healthy volunteers and patients with lymphoproliferative disorders by PCR-ELISA. Leuk Res. 1999;23(7):625-30.

[158] Barozzi P, Luppi M, Masini L, Marasca R, Savarino M, Morselli M, Ferrari MG, Bevini M, Bonacorsi G, Torelli G. Lymphotropic herpes virus (EBV, HHV-6, HHV-8) DNA sequences in HIV negative Castleman's disease. Clin Mol Pathol. 1996;49(4):M232-5.

[159] Krueger GR, Guenther A, Knuefermann R, Kluppelberg U, Luka J, Pearson GR, Ablashi DV, Juecker M, Tesch H. Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens as compared to oncogenes met and fes, tumor suppressor gene product p53, and interleukins 2 and 6. In Vivo. 1994;8(4):501-16.

[160] Valente G, Secchiero P, Lusso P, Abete MC, Jemma C, Reato G, Kerim S, Gallo RC, Palestro G. Human herpesvirus 6 and Epstein-Barr virus in Hodgkin's disease: a controlled study by polymerase chain reaction and in situ hybridization. Am J Pathol. 1996;149(5):1501-10.

[161] Collot S, Petit B, Bordessoule D, Alain S, Touati M, Denis F, Ranger-Rogez S. Real-time PCR for quantification of human herpesvirus 6 DNA from lymph nodes and saliva. J Clin Microbiol. 2002;40(7):2445-51.

[162] Lacroix A, Jaccard A, Rouzioux C, Piguet C, Petit B, Bordessoule D, Ranger-Rogez S. HHV-6 and EBV DNA quantitation in lymph nodes of 86 patients with Hodgkin's lymphoma. J Med Virol. 2007;79(9):1349-56.

[163] Kashanchi F, Araujo J, Doniger J, Muralidhar S, Hoch R, Khleif S, Mendelson E, Thompson J, Azumi N, Brady JN, Luppi M, Torelli G, Rosenthal LJ. Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53. Oncogene. 1997;14(3):359-67.

[164] Lacroix A, Collot-Teixeira S, Mardivirin L, Jaccard A, Petit B, Piguet C, Sturtz F, Preux PM, Bordessoule D, Ranger-Rogez S. Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein. Clin Cancer Res. 2010;16(19):4711-21.

[165] Siddon A, Lozovatsky L, Mohamed A, Hudnall SD. Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma. Br J Haematol. 2012;158(5):635-43.

[166] Carbone A, Dolcetti R, Gloghini A, Maestro R, Vaccher E, di Luca D, Tirelli U, Boiocchi M. Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: a comparative study. Hum Pathol. 1996;27(2):133-46.

[167] Braun DK, Pellett PE, Hanson CA. Presence and expression of human herpesvirus 6 in peripheral blood mononuclear cells of S100-positive, T cell chronic lymphoproliferative disease. J Infect Dis. 1995;171(5):1351-5.

[168] Lu C, Zeng Y, Huang Z, Huang L, Qian C, Tang G, Qin D. Human herpesvirus 6 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus. Am J Pathol. 2005;166(1):173-83.

[169] Josephs SF, Buchbinder A, Streicher HZ, Ablashi DV, Salahuddin SZ, Guo HG, Wong-Staal F, Cossman J, Raffeld M, Sundeen J. Detection of human B-lymphotropic virus (human herpesvirus 6) sequences in B cell lymphoma tissues of three patients. Leukemia. 1988;2(3):132-5.

[170] Zhou Y, Attygalle AD, Chuang SS, Diss T, Ye H, Liu H, Hamoudi RA, Munson P, Bacon CM, Dogan A, Du MQ. Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load. Br J Haematol. 2007;138(1):44-53.

[171] Strong MJ, O'Grady T, Lin Z, Xu G, Baddoo M, Parsons C, Zhang K, Taylor CM, Flemington EK. Epstein-Barr virus and human herpesvirus 6 detection in a non-Hodgkin's diffuse large B-cell lymphoma cohort by using RNA sequencing. J Virol. 2013;87(23):13059-62.

[172] Luppi M, Marasca R, Barozzi P, Artusi T, Torelli G. Frequent detection of human herpesvirus-6 sequences by polymerase chain reaction in paraffin-embedded lymph nodes from patients with angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Leuk Res. 1993;17(11):1003-11.

[173] Campioni D, Gentili V, Cavazzini F, Bortolotti D, Nacheva EP, Cuneo A, Di Luca D, Rizzo R. Detection of inherited chromosomally integrated HHV-6 (ciHHV-6) in a marker chromosome. Eur J Haematol. 2017;98(6):635-7.

[174] Zhang E, Cotton VE, Hidalgo-Bravo A, Huang Y, Bell AJ, Jarrett RF, Wilkie GS, Davison AJ, Nacheva EP, Siebert R, Majid A, Kelpanides I, Jayne S, Dyer MJ, Royle NJ. HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6A from the telomere of chromosome 19q. Sci Rep. 2016;6:22730.

[175] Seror E, Coquerel B, Gautheret-Dejean A, Ballerini P, Landman-Parker J, Leverger G, Schneider P, Vannier JP. Quantitation of Human herpes virus 6 genome in children with acute lymphoblastic leukemia. J Med Virol. 2008;80(4):689-93.

[176] Mori S, Sugahara K, Uemura A, Akamatsu N, Hirakata Y, Murata K, Hasegawa H, Yamada Y, Kamihira S. Usefulness of a comprehensive PCR-based assay for human herpes viral DNA in blood mononuclear cell samples. Lab Hematol. 2005;11(3):163-70.

[177] Levine PH, Ablashi DV, Saxinger WC, Connelly RR. Antibodies to human herpes virus-6 in patients with acute lymphocytic leukemia. Leukemia. 1992;6(11):1229-31.

[178] Schlehofer B, Blettner M, Geletneky K, Haaf HG, Kaatsch P, Michaelis J, Mueller-Lantzsch N, Niehoff D, Winkelspecht B, Wahrendorf J, Schlehofer JR. Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia. Int J Cancer. 1996;65(5):584-90.

[179] Steininger C, Rassenti LZ, Vanura K, Eigenberger K, Jäger U, Kipps TJ, Mannhalter C, Stilgenbauer S, Popow-Kraupp T. Relative seroprevalence of human herpes viruses in patients with chronic lymphocytic leukaemia. Eur J Clin Invest. 2009;39(6):497-506.

[180] Faten N, Agnès GD, Nadia BF, Nabil AB, Monia Z, Abderrahim K, Henri A, Salma F, Mahjoub A. Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study. Infect Agent Cancer. 2012;7(1):31.

[181] Hermouet S, Sutton CA, Rose TM, Greenblatt RJ, Corre I, Garand R, Neves AM, Bataille R, Casey JW. Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma. Leukemia. 2003;17(1):185-95.

[182] Krueger GR, Kudlimay D, Ramon A, Klueppelberg U, Schumacher K. Demonstration of active and latent Epstein-Barr virus and human herpevirus-6 infections in bone marrow cells of patients with myelodysplasia and chronic myeloproliferative diseases. In Vivo. 1994;8(4):533-42.

[183] Morales-Sánchez A, Pompa-Mera EN, Fajardo-Gutiérrez A, Alvarez-Rodríguez FJ, Bekker-Méndez VC, Flores-Chapa Jde D, Flores-Lujano J, Jiménez-Hernández E, Peñaloza-González JG, Rodríguez-Zepeda MC, Torres-Nava JR, Velázquez-Aviña MM, Amador-Sánchez R, Alvarado-Ibarra M, Reyes-Zepeda N, Espinosa-Elizondo RM, Pérez-Saldivar ML, Núñez-Enríquez JC, Mejía-Aranguré JM, Fuentes-Pananá EM. EBV, HCMV, HHV6, and HHV7 screening in bone marrow samples from children with acute lymphoblastic leukemia. Biomed Res Int. 2014;2014:548097.

[184] Krueger GR, Klueppelberg U, Hoffmann A, Ablashi DV. Clinical correlates of infection with human herpesvirus-6. In Vivo. 1994;8(4):457-85.

[185] Krueger GR, Ferrer Argote V. A unifying concept of viral immunopathogenesis of proliferative and aproliferative diseases (working hypothesis). In Vivo. 1994;8(4):493-9.