scholarly journals Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris

2015 ◽  
Vol 112 (26) ◽  
pp. 8058-8063 ◽  
Author(s):  
Annie Gravel ◽  
Isabelle Dubuc ◽  
Guillaume Morissette ◽  
Ruth H. Sedlak ◽  
Keith R. Jerome ◽  
...  
Keyword(s):  
Risk Factor ◽  
Angina Pectoris ◽  
Large Scale ◽  
Germ Line ◽  
Human Herpesvirus ◽  
Bonferroni Correction ◽  
Human Herpesvirus 6 ◽  
Large Scale Analysis ◽  
Herpesvirus 6 ◽  
Germ Line Transmission

Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6− subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm–Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm–Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6− subjects (P = 0.017; 95% CI, 1.73–6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23–7.15). Analyses of telomere lengths between iciHHV-6− without angina, iciHHV-6− with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6− subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.

Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7

1997 ◽  
Vol 8 (1) ◽  
pp. 24-31 ◽  
Author(s):  
K Takahashi ◽  
M Suzuki ◽  
Y Iwata ◽  
S Shigeta ◽  
K Yamanishi ◽  
...  
Keyword(s):  
Large Scale ◽  
Human Herpesvirus ◽  
Tetrazolium Salt ◽  
Human Herpesvirus 6 ◽  
Phosphonoformic Acid ◽  
Highly Sensitive ◽  
Acyclic Nucleoside ◽  
Herpesvirus 6 ◽  
Acyclic Nucleoside Phosphonate ◽  
Large Scale Screening

We have developed a new sensitive enzyme immunoassay (EIA) and MTT (tetrazolium salt) assay for screening compounds against two variants of human herpesvirus 6 (HHV-6A, HHV-6B) and human herpesvirus 7 (HHV-7) and evaluated the anti-HHV-6 and HHV-7 activity of a series of anti-herpesvirus compounds and acyclic nucleoside phosphonate analogues. The results indicate that the pattern of activity of these compounds against these betaherpesviruses is similar to that for human cytomegalovirus (HCMV). The highest potency and selectivity against the two variants of HHV-6 and HHV-7 was demonstrated by S2242 (N7-isomer of 6-deoxy-ganciclovir). Also, ganciclovir (GCV), foscarnet, (phosphonoformic acid; PFA) and the acyclic nucleoside phosphonate analogues such as cidofovir (HPMPC) exhibited selective inhibitory activity against these viruses. Thymidine kinase (TK)-dependent drugs (acyclovir, ACV; brivudin, BVDU; and sorivudine, BVaraU) showed little, if any, activity. These results suggest a structural homology of the DNA polymerase and a lack of TK gene among these three betaherpesviruses (HHV-6, HHV-7 and HCMV). The finding that HHV-7 was highly sensitive to GCV also suggests that HHV-7 may have an HCMV-UL97-homologue gene for the phosphorylation of GCV. The present EIA method is more rapid and sensitive than the previously reported procedures and could be useful for the large-scale screening of compounds against HHV-6 and HHV-7.

scholarly journals Identification of Chromosomally Integrated Human Herpesvirus 6 by Droplet Digital PCR

2014 ◽  
Vol 60 (5) ◽  
pp. 765-772 ◽  
Author(s):  
Ruth Hall Sedlak ◽  
Linda Cook ◽  
Meei-Li Huang ◽  
Amalia Magaret ◽  
Danielle M Zerr ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Germ Line ◽  
Human Herpesvirus ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Cell Transplant ◽  
Plasma Samples ◽  
Human Herpesvirus 6 ◽  
Hematopoietic Stem ◽  
Herpesvirus 6

Abstract BACKGROUND Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests. METHODS A droplet digital PCR (ddPCR) assay was developed to identify ciHHV-6 in cellular patient samples by precisely determining the ratio of HHV-6 to cellular DNA. We validated the assay on confirmed ciHHV-6 patient samples and a cell line derived from a ciHHV-6 patient, and we analyzed hematopoietic stem cell transplant patients suspected of having ciHHV-6. We additionally evaluated whether the assay could be applied to stored plasma samples from a study of clinical correlates of HHV-6. RESULTS The ddPCR assay accurately identified ciHHV-6 in cellular samples (buffy coat, peripheral blood mononuclear cells), giving a ratio very close to 1 HHV-6/cell [mean (SD), 1.02 (0.03)] in fluorescence in situ hybridization–confirmed sample). In stored plasma samples, the assay performance was set by design to have 100% sensitivity, which resulted in 82% specificity for ciHHV-6. CONCLUSIONS The possibility of ciHHV-6 is often overlooked in patients with detectable HHV-6 viral loads by quantitative PCR. Our ddPCR test provides rapid and accurate laboratory identification of ciHHV-6 from easily obtained cellular samples. In addition, the assay provides excellent sensitivity and specificity using stored plasma samples, facilitating retrospective analysis of the clinical significance of ciHHV-6.

Inherited Chromosomally Integrated Human Herpesvirus 6 Is a Risk Factor for Spontaneous Abortion

2020 ◽  
Author(s):  
Hiroki Miura ◽  
Yoshiki Kawamura ◽  
Tamae Ohye ◽  
Fumihiko Hattori ◽  
Kei Kozawa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Spontaneous Abortion ◽  
Human Herpesvirus ◽  
Human Herpesvirus 6 ◽  
Pregnancy History ◽  
Copy Numbers ◽  
History Of ◽  
Herpesvirus 6 ◽  
Dna Copy Numbers ◽  
Index Cases

Abstract Background Human herpesvirus 6 (HHV-6) can be genetically transmitted from parent to child as inherited chromosomally integrated HHV-6 (iciHHV-6). HHV-6 reactivation occurs in pregnant women with iciHHV-6. We found no sex differences in the frequency of index cases with iciHHV-6 but inheritance from the father was more common. We evaluated the association between iciHHV-6 status and spontaneous abortion. Methods iciHHV-6 was confirmed by high viral DNA copy numbers in whole blood and somatic cells. The origin of integrated viral genome, paternal or maternal, was examined using the same method. The pregnancy history of 23 mothers in families with iciHHV-6 and 285 mothers in families without iciHHV-6 was abstracted. Results Of 23 iciHHV-6 index cases, 8 mothers and 15 fathers had iciHHV-6. Spontaneous abortion rates in mothers with and mothers without/fathers with iciHHV-6 and mothers in families without iciHHV-6 were 27.6%, 10.3%, and 14.8%, respectively (P = .012). Mothers with iciHHV-6 (odds ratio [OR], 6.41; 95% confidence interval [CI], 1.10–37.4) and maternal age at the most recent pregnancy ≥40 years (OR, 3.91; 95% CI, 1.30–11.8) were associated with 2 or more spontaneous abortions. Conclusions Mothers with iciHHV-6 is a risk factor for spontaneous abortion.

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