Review Part 3: Human herpesvirus-6 in multiple non-neurological diseases

HHV-6 Foundation, Santa Barbara, California, USA.
Journal of Medical Virology (Impact Factor: 2.35). 11/2010; 82(11):1903-10. DOI: 10.1002/jmv.21860
Source: PubMed


J. Med. Virol. 82:1903–1910, 2010. © 2010 Wiley-Liss, Inc.

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    • "(E) The complete HHV-6B genome is present in the CEPH1375 family. Overlapping amplicons (1–31) covering the unique portion of the HHV-6B genome and the DRs (amplicon 32, without T1 and T2) were generated from CEPH1375.02. Each amplicon is the expected size showing there are no gross rearrangements of the integrated viral genome. "
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    ABSTRACT: Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integrated copy of human herpesvirus 6 (CI-HHV-6), but the consequences of integration for the virus and for the telomere with the insertion are unknown. Here we show that the telomere on the distal end of the integrated virus is frequently the shortest measured in somatic cells but not the germline. The telomere carrying the CI-HHV-6 is also prone to truncations that result in the formation of a short telomere at a novel location within the viral genome. We detected extra-chromosomal circular HHV-6 molecules, some surprisingly comprising the entire viral genome with a single fully reconstituted direct repeat region (DR) with both terminal cleavage and packaging elements (PAC1 and PAC2). Truncated CI-HHV-6 and extra-chromosomal circular molecules are likely reciprocal products that arise through excision of a telomere-loop (t-loop) formed within the CI-HHV-6 genome. In summary, we show that the CI-HHV-6 genome disrupts stability of the associated telomere and this facilitates the release of viral sequences as circular molecules, some of which have the potential to become fully functioning viruses.
    Nucleic Acids Research 09/2013; 42(1). DOI:10.1093/nar/gkt840 · 9.11 Impact Factor
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    • ", species Human herpesvirus 4; EBV or HHV-4) are among the viruses that have been frequently associated with CFS [Komaroff, 1988, 2006; Kogelnik et al., 2006]. EBV and HHV-6 are lymphotrophic and produce latent infections with immunomodulatory effects [Ambinder, 2003; Krueger and Ablashi, 2003; Ambinder and Lin, 2005] In addition, HHV-6 has been found to be neurotropic [Ablashi et al., 2010; Flamand et al., 2010; Yao et al., 2010] and can reside in neurons [Fotheringham et al., 2008] and cardiac myocytes [Kuhl et al., 2005; Leveque et al., 2011] in a semi-active state without evidence of continued infection in the plasma compartment . HHV-6 has been associated with cognitive decline in hematopoietic stem cell transplantation, and it has been reported to cause encephalitis in 8–14% of umbilical cord blood transplant patients [Mori et al., 2010; Hill et al., 2012]. "
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    ABSTRACT: Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160. Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non-responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response. J. Med. Virol. 84:1967-1974, 2012. © 2012 Wiley Periodicals, Inc.
    Journal of Medical Virology 12/2012; 84(12):1967-74. DOI:10.1002/jmv.23411 · 2.35 Impact Factor
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    • "Thus, in solid-organ transplant recipients, the reactivation of HHV-6 is frequent and usually asymptomatic. However, clinical complications may occur, including fever, encephalitis, rash, pneumonitis, gastrointestinal infection, hepatitis, and graft rejection [Ablashi et al., 2010]. Hematopoietic stem cell recipients constitute the major population for HHV-6-associated diseases such as encephalitis, delayed engraftment, myelosuppression, and graft versus host disease. "
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    ABSTRACT: Human herpesvirus-6 and -7 (HHV-6 and HHV-7) may lead to pathological manifestations in renal transplant recipients. The aim of this study was to investigate beta-herpesvirus infections in 50 adult kidney transplant recipients after transplantation to examine the effect, interactions, and pathogenic consequences of infection and the effect of immunosuppressive regimens and Human cytomegalovirus (HCMV) prophylaxis with VACV. Beta-herpesviruses loads in the blood of 50 adult kidney transplant recipients over a 6-month period after transplantation and 198 blood donors were determined using polymerase chain reaction. The rate of HHV-6 detection in peripheral mononuclear cells (PBMCs) was higher in patients with end-stage renal disease and during the post-transplantation follow-up than in healthy subjects (33% and 68% vs. 12%, respectively). The detection rate of HHV-7 in PBMCs was similar between patients, both before grafting and during the follow-up for transplant recipients (69% and 88%, respectively), and healthy subjects (78%), and correlated with the number of lymphocytes. HCMV in plasma was detected only in patients during the post-transplant period (24%). VACV prophylaxis had no negative effect on the replication of HHV-6 or HHV-7, and univariate analyses demonstrated associations between HHV-6 infection and acute graft rejection [Odds ratio (OR) = 2.94, 95% confidence interval (CI), 1.05-8.2, P = 0.04], and between HHV-7 infection and cholestasis [OR = 2.61 (95% CI, 1.08-6.3), P = 0.03]. Immunosuppressive regimens had no effect on beta-herpesviruses infections. This study revealed the differing behavior of HCMV, HHV-6, and HHV-7 in kidney transplant recipients, and confirmed the association of HHV-6 with graft rejection.
    Journal of Medical Virology 03/2012; 84(3):450-6. DOI:10.1002/jmv.23206 · 2.35 Impact Factor
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