Chromosomal integration of HHV-6A during non-productive viral infection

Gulve, Nitish; Frank, Celina; Klepsch, Maximilian; Prusty, Bhupesh K.

doi:10.1038/s41598-017-00658-y

Cited by 17 publications

(19 citation statements)

References 27 publications

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“…Although unusual, it is important to note that there has recently been a single report that describes the integration of HHV-6 in non-telomeric regions of the chromosome [ 49 ]. Sequencing of the integration site and fluorescent in situ hybridization confirmed integration events outside of the telomeres in four independent cell lines and at least one iciHHV-6 individual.…”

Section: Integration Of Hhv-6 In Telomeres During Latencymentioning

confidence: 99%

“…Multiplex ligation-dependent probe amplification (MLPA) analyses of five iciHHV-6B cases indicated direct repeats (DR) copy number greater than or less than two [ 50 ]. Similarly, when the DR copy number was assessed using quantitative polymerase chain reaction (qPCR) analysis, a DR copy number of greater than two was reported for numerous individuals with either iciHHV-6A or iciHHV-6B [ 49 ]. Furthermore, the DR copy number was reported to fluctuate in iciHHV-6 individuals over a span of three years.…”

Section: Structure and Orientation Of The Telomere-integrated Viramentioning

confidence: 99%

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Latency, Integration, and Reactivation of Human Herpesvirus-6

Pantry

Medveczky

2017

Viruses

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Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. In about 1% of the human population, human herpes virus-6 (HHV-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is called inherited chromosomally integrated HHV-6 (iciHHV-6). This review will cover the history of HHV-6 and recent works that define the biological differences between HHV-6A and HHV-6B. Additionally, HHV-6 integration and inheritance, the capacity for reactivation and superinfection of iciHHV-6 individuals with a second strain of HHV-6, and the role of hypomethylation of human chromosomes during integration are discussed. Overall, the data suggest that integration of HHV-6 in telomeres represent a unique mechanism of viral latency and offers a novel tool to study not only HHV-6 pathogenesis, but also telomere biology. Paradoxically, the integrated viral genome is often defective especially as seen in iciHHV-6 harboring individuals. Finally, gaps in the field of HHV-6 research are presented and future studies are proposed.

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Section: Integration Of Hhv-6 In Telomeres During Latencymentioning

confidence: 99%

Section: Structure and Orientation Of The Telomere-integrated Viramentioning

confidence: 99%

Latency, Integration, and Reactivation of Human Herpesvirus-6

Pantry

Medveczky

2017

Viruses

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“…Serum was isolated at the site of blood collection and was shipped to the laboratory for further analysis. Quantitative PCR (qPCR) assays for HHV-6 DNA (U94) and HHV-7 are previously described (17)(18)(19).…”

Section: Methodsmentioning

confidence: 99%

Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

et al. 2020

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)-6 and HHV-7 are two infectious triggers for which evidence has been growing. To understand possible causative role of HHV-6 in ME/CFS, metabolic and antiviral phenotypes of U2-OS cells were studied with and without chromosomally integrated HHV-6 and with or without virus reactivation using the histone deacetylase inhibitor trichostatin-A. Proteomic analysis was conducted by pulsed stable isotope labeling by amino acids in cell culture analysis. Antiviral properties that were induced by HHV-6 transactivation were studied in virus-naive A549 cells challenged by infection with influenza-A (H1N1) or HSV-1. Mitochondria were fragmented and 1-carbon metabolism, dUTPase, and thymidylate synthase were strongly induced by HHV-6 reactivation, whereas superoxide dismutase 2 and proteins required for mitochondrial oxidation of fatty acid, amino acid, and glucose metabolism,

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“…In these cases, the single-DR genomic “scar” potentially resulting from excision and reactivation was not studied. One subject with apparent integration of a single DR in a non-telomeric location has been described {Gulve, 2017}. Two subjects with single DRs, potentially in the germline telomere, have been mentioned in discussion, but details are lacking {Huang, 2014}.…”

Section: Introductionmentioning

confidence: 99%

Endogenization and excision of human herpesvirus 6 in human genomes

Liu

Kosugi

Koide

et al. 2019

Preprint

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36The genome of human herpesvirus 6 (HHV-6) is integrated within the nuclear genome of 37 about 1% of humans, but how this came about is not clear. HHV-6 integrates into telomeres, 38 and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is 39 located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-40interacting RNAs (piRNAs). piRNAs block integration of transposons in the germline, so 41 piRNA-mediated repression of HHV-6 integration has been suspected. Whether integrated 42 HHV-6 can reactive into an infectious virus is also uncertain. In vitro, recombination of the 43 viral genome along its terminal direct repeats (DRs) leads to excision from the telomere and 44 viral reactivation, but the expected single DR "scar" has not been described in vivo. We 45 analyzed whole-genome sequencing (WGS) data from 13,040 subjects, including 7,485 from 46 Japan. We found an association between integrated HHV-6 and polymorphisms on chr22q in 47Human herpesvirus 6 (HHV-6) infects most people during childhood, usually only causing 63 fever and rash. Reactivation of HHV-6 has been linked to a number of neurological diseases 64 including encephalitis, Alzheimer's disease and multiple sclerosis. However, about 1% of 65 people are born with the HHV-6 genome present within their genome, included in the end 66"cap" of one of their 46 chromosomes. Little is known about how and when HHV-6 genomes 67 entered human genomes, whether or not they still do, and whether or not this poses risk for 68 virus reactivation. We looked for HHV-6 in genome sequences from over 13,000 people. 69

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Chromosomal integration of HHV-6A during non-productive viral infection

Cited by 17 publications

References 27 publications

Latency, Integration, and Reactivation of Human Herpesvirus-6

Latency, Integration, and Reactivation of Human Herpesvirus-6

Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Endogenization and excision of human herpesvirus 6 in human genomes

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