Chromosomally integrated human herpesvirus 6 in heart failure: Prevalence and treatment

European Journal of Heart Failure

Volumn 17, Issue 1, 2015, Pages 9-19

  Kühl, Uwe ^a   Lassner, Dirk ^b   Wallaschek, Nina ^c   Gross, Ulrich M ^b   Krueger, Gerhard R F ^d   Seeberg, Bettina ^a   Kaufer, Benedikt B ^c   Escher, Felicitas ^a   Poller, Wolfgang ^a   Schultheiss, Heinz Peter ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b Institut Kardiale Diagnostik und Therapie (IKDT)   (Germany)

^c FREIE UNIVERSITÄT BERLIN   (Germany)

^d UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

Cardiomyopathy; Chromosomally integrated human herpesvirus 6; Myocarditis; Treatment

Indexed keywords

GANCICLOVIR; MESSENGER RNA; PANTOPRAZOLE; VALGANCICLOVIR; ANTIVIRUS AGENT; VIRUS DNA;

ADENOVIRUS INFECTION; ADULT; AGED; ARTICLE; CHROMOSOMALLY INTEGRATED HUMAN HERPESVIRUS 6; DNA REPLICATION; DRUG MEGADOSE; DRUG SUBSTITUTION; DRUG WITHDRAWAL; ELECTRON MICROSCOPY; ENTEROVIRUS INFECTION; EPSTEIN BARR VIRUS INFECTION; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE DOSAGE; GENOTYPE; HEART; HEART FAILURE; HEART MUSCLE BIOPSY; HEART MUSCLE CELL; HEARTBURN; HERPES VIRUS INFECTION; HUMAN; HUMAN HERPESVIRUS 6; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MIXED INFECTION; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; POLYMERASE CHAIN REACTION; PREVALENCE; PRIORITY JOURNAL; PROSPECTIVE STUDY; RECURRENT VIRUS INFECTION; RNA SYNTHESIS; SPECIES DISTRIBUTION; TREATMENT RESPONSE; VIRUS LOAD; VIRUS MYOCARDITIS; VIRUS PARTICLE; VIRUS REACTIVATION; VIRUS REPLICATION; CARDIOMYOPATHY, DILATED; COHORT ANALYSIS; GENETICS; GERMANY; HEART MUSCLE; METABOLISM; MYOCARDITIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ROSEOLOVIRUS INFECTIONS; TREATMENT OUTCOME; ULTRASTRUCTURE; VIROLOGY; VIRUS DNA CELL DNA INTERACTION;

ADULT; ANTIVIRAL AGENTS; CARDIOMYOPATHY, DILATED; COHORT STUDIES; DNA, VIRAL; FEMALE; GANCICLOVIR; GERMANY; HEART; HEART FAILURE; HERPESVIRUS 6, HUMAN; HUMANS; MALE; MICROSCOPY, ELECTRON; MIDDLE AGED; MYOCARDITIS; MYOCARDIUM; PREVALENCE; PROSPECTIVE STUDIES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; ROSEOLOVIRUS INFECTIONS; TREATMENT OUTCOME; VIRAL LOAD; VIRUS INTEGRATION;

EID: 84921368979     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1002/ejhf.194     Document Type: Article

References (36)

1. 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 IT, 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. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol 2012;22:144-155.
2. Krueger GRF, Rojo J, Buja LM, Lassner D, Kuehl U. Human herpesvirus-6 (HHV-6) is a possible cardiac pathogen: an immunohistological and ultrastructural study. Hosp Gen 2008;71:187-191.
3. Caruso A, Rotola A, Comar M, Favilli F, Galvan M, Tosetti M, Campello C, Caselli E, Alessandri G, Grassi M, Garrafa E, Cassai E, Di Luca D. HHV-6 infects human aortic and heart microvascular endothelial cells, increasing their ability to secrete proinflammatory chemokines. J Med Virol 2002;67:528-533.
4. Lautenschlager I, Razonable RR. Human herpesvirus-6 infections in kidney, liver, lung, and heart transplantation: review. Transplant Int 2012;25:493-502.
5. Ratnamohan VM, Chapman J, Howse H, Bovington K, Robertson P, Byth K, Allan R, Cunningham AJ. Cytomegalovirus and human herpesvirus 6 both cause viral disease after renal transplantation. Transplantation 1998;66:877-882.
6. Fotheringham J, Akhyani N, Vortmeyer A, Donati D, Williams E, Oh U, Bishop M, Barrett J, Gea-Banacloche J, Jacobson S. Detection of active human herpesvirus-6 infection in the brain: correlation with polymerase chain reaction detection in cerebrospinal fluid. J Infect Dis 2007; 195:450-454.
7. Hall CB, Caserta MT, Schnabel KC, Long C, Epstein LG, Insel RA, Dewhurst S. Persistence of human herpesvirus 6 according to site and variant: possible greater neurotropism of variant A. Clin Infect Dis 1998;26:132-137.
8. Kühl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with 'idiopathic' left ventricular dysfunction. Circulation 2005;111:887-893.
9. Leong HN, Tuke PW, Tedder RS, Khanom AB, Eglin RP, Atkinson CE, Ward KN, Griffiths PD, Clark DA. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol 2007;79:45-51.
10. Ward KN, Thiruchelvam AD, Couto-Parada X. Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection of variants A and B. J Med Virol 2005;79:563-570.
11. 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. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci USA 2010;107:5563-5568.
12. Arbuckle JH, Pantry SN, Medveczky MM, Prichett J, Loomis KS, Ablashi D, Medveczky PG. Mapping thetelomere integrated genome of human herpesvirus 6A and 6B. Virology 2013;442:3-11.
13. Hall CB, Caserta MT, Schnabel K, Shelley LM, Marino AS, Carnahan JA, Yoo C, Lofthus GK, McDermott MP. Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics 2008;122:513-520.
14. Flammand LL, Krueger GRF, Ablashi DV, eds. Human Herpesviruses HHV-6A, HHV-6B, and HHV-7: Diagnosis and Clinical Management. Amsterdam: Elsevier; 2014.
15. Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, Kurahashi H, Yoshikawa T, Katano H, Inuoue N, Imai K, Takagi M, Morio T, Mizutani S. Molecular and virological evidence of viral activation from chromosomally integreted human herpesvirus 6A in a patient with x-linked severe combined immunodeficiency. Clin Infect Dis 2014;59:545-548.
16. Gravel A, Hall CB, Flammand L. Sequence analysis of transplacentally acquired human herpesvirus 6 DNA is consistent with transmission of a chromosomally integrated reactivated virus. J Infect Dis 2013;207:1585-1589.
17. Kühl U, Lassner D, Pauschinger M, Gross UM, Seeberg B, Noutsias M, Poller W, Schultheiss HP. Prevalence of erythrovirus genotypes in the myocardium of patients with dilated cardiomyopathy. J Med Virol 2008;80:1243-1251.
18. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol 1987;18:619-624.
19. Kühl U, Noutsias M, Seeberg B, Schultheiss HP. Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart 1996;75:295-300.
20. Noutsias M, Seeberg B, Schultheiss HP, Kuhl U. Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 1999;99:2124-2131.
21. Pellett PE, Sanchez-Martinez D, Dominguez G, Black JB, Anton E, Greenamoyer C, Dambaugh TR. A strongly immunoreactive virion protein of human herpesvirus 6 variant B strain Z29: identification and characterization of the gene and mapping of a variant-specific monoclonal antibody reactive epitope. Virology 1993;195:521-531.
22. Kaufer BB. Detection of integrated herpesvirus genomes by fluorescence in situ hybridization (FISH). Methods Mol Biol 2013;1064:141-152.
23. Kühl U, Lassner D, Dorner A, Rohde BM, Escher F, Seeberg B, Hertel E, Tschope C, Gross U, Poller W, Schultheiss HP. A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression. Basic Res Cardiol 2013;108:372-382.
24. Potenza L, Barozzi P, Masetti M, Pecorari M, Bresciani P, Gautheret-Dejean A, Riva G, Vallerini D, Tagliazucchi S, Codeluppi M, Di Benedetto F, Gerunda GE, Narni F, Torelli G, Luppi M. Prevalence of human herpesvirus-6 chromosomal integration (CIHHV-6) in Italian solid organ and allogeneic stem cell transplant patients. Am J Transplant 2009;9:1690-1697.
25. Morissette G, Flamand L. Herpesviruses and chromosomal integration. J Virol 2010;84:12100-12109.
26. Hall CB, Caserta MT, Schnabel KC, Shelley LM, Carnahan JA, Marino AS, Yoo C, Lofthus GK. Transplacental congenital human herpesvirus 6 infection caused by maternal chromosomally integrated virus. J Infect Dis 2010;201:505-507.
27. Huang Y, Hidalgo-Bravo A, Zhang E, Cotton VE, Mendez-Bermudez A, Wig G, Medina-Calzada Z, Neumann R, Jeffreys AJ, Winney B, Wilson JF, Clark DA, Dyer MJ, Royle NJ. Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome. Nucleic Acid Res 2013;42:315-327.
28. Prusty BK, Krone G, Rudel T. Reactivation of chromosomally integrated human herpesvirus-6 by telomeric circle formation. PLOS Genet 2013;9:e1004033.
29. Pantry SN, Medveczky MM, Arbucle JH, Luka J, Montoya JG, Hu J, Renne R, Peterson D, Pritchett JC, Ablashi DV, Medveczky PG. Persistent human herpesvirus-6 infection in patients with an inherited form of the virus. J Med Virol 2013;85:1940-1949.
30. Schmidt-Lucke C, Spillmann F, Bock T, Van Linthout S, Kühl U, Schultheiss HP, Tschoepe C. Interferon-beta modulates endothelial damage in patients with cardiac persistence of parvovirus B19V. J Infectious Dis 2010;201:936-945.
31. Reynaud JM, Jegou 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;88:5421-5436.
32. Dewin DR, Catusse J, Gompels U. Identification and caracterization of U83A viral chemokine, a broad and potent beta-chemokine agonist for human CCRs with unique selectivity and inhibition by spliced isoforms. Immunology 2006;176:544-556.
33. Montoya JG, Neely MN, Gupta S, Lunn MR, Loomis KS, Pritchett JC, Polsky B, Medveczky PG. Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction. J Clin Virol 2012;55:40-45.
34. Watt T, Oberfoell S, Balise R, Lunn MR, Kar AK, Merrihew L, Bhangoo MS, Montoya JG. Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers. J Med Virol 2012;84:1967-1974.
35. Troy SB, Blackburn BG, Yeom K, Caufield AKF, Bhangoo MS, Montoya JG. Immunocompetent adult with chromosomally integrated human herpesvirus 6 and clinical response to treatment with foscanet plus ganciclivir. Clin Inf Dis 2008;47:e93-e96.
36. Wittekind B, Berger A, Porto L, Grüttner HP, Becker M, Lehrnbecher T. Human herpes virus-6 DNA in cerebrospinal fluid of children undergoing therapy for acute leukemis. Br J Haematol 2009;145:533-550.