A repeat sequence, GGGTTA, is shared by DNA of human herpesvirus 6 and Marek's disease virus

Kusumoto, Masahiko; Harada, Hiroshi; Takahashi, Michiaki; Tanaka, Akiko; Hayashi, Masanobu; Nonoyama, Meihan; Josephs, S.F.; Buchbinder, Aby; Schächter, François; Ablashi, Dharam V.

doi:10.1128/jvi.62.12.4824-4827.1988

Cited by 73 publications

(27 citation statements)

References 28 publications

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“…Chromosomal rearrangement has been reported in segments distal to the telomere unique sequences in cases with constitu-tional abnormalities [Flint et al, 1995] and in an infant with thrombocytopenia [Gribble et al, 2000]. Interestingly, another herpesvirus, Marek's disease virus, also contains telomere-like sequences in its genome [Kishi et al, 1988] and has been shown to integrate into avian chromosomes at several different telomeric sites [Delecluse and Hammerschmidt, 1993]. Finally, HHV-6 is unique amongst the human herpesviruses in that it contains a gene that encodes a homologue of the adenoassociated virus (AAV) rep gene [Thomson et al, 1991].…”

Section: Discussionmentioning

confidence: 99%

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal Sites

Nacheva

Ward

Brazma

et al. 2008

Journal of Medical Virology

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Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal integration sites of human herpesvirus 6 (HHV-6) in phytohemagglutinin-stimulated leukocytes and B lymphocytes from Epstein-Barr virus transformed lymphoblastoid cell lines (LCLs). Five different chromosomal integration sites were found in nine individuals. Only one site was identified in each individual, each site was in the vicinity of the telomeric region and was on either the p or q arm of only one of the two chromosome homologues. The sites were 9q34.3, 10q26.3, 11p15.5, 17p13.3, and 19q 13.4, of which three have not been previously identified. For 9q34.3 the site of integration was further mapped using a locus-specific probe for 9q34.3 together with a pan-telomeric probe and both co-localized with the HHV-6 signal. Similarly an arm-specific telomeric probe for 19q co-localized with the HHV-6 signal. It was therefore concluded that the site of integration is actually within the telomere. The number of viral DNA copies/cell was calculated in blood, LCL cells and hair follicles and was one or more in every case for each of the nine individuals. This result was confirmed by FISH where 100% of cells gave an HHV-6 signal. These findings add to previous reports suggesting that integrated HHV-6 DNA is found in every cell in the body and transmitted vertically. Finally, including our data, worldwide seven different chromosomal sites of HHV-6 integration have now been identified. Large epidemiological studies of chromosomal integration are required to identify further telomeric sites, geographical or racial variation and possible clinical consequences.

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Section: Discussionmentioning

confidence: 99%

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal Sites

Nacheva

Ward

Brazma

et al. 2008

Journal of Medical Virology

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“…The MDV integration sites, which are not specific, are located preferentially at the telomere of the involved chromosomes [Delecluse and Hammerschmidt, 1993;Delecluse et al, 1993b1. HHVS also integrates in a telomeric region of chromosome 17 and shares with MDV the presence of the (GGGTTA), repeated motif, which in HHV-6 lies in the right extremities of the direct repeat units [Kishi et al, 1988;Martin et al, 19911, more precisely about 40 nucleotides upstream the right end of the viral chromosome [Thomson et al, 19941. It is notable that the (GGGTTA), repeat is highly conserved in the telomeres of all vertebrate chromosomes [Meyne et al, 19891. Obviously the integration of EBV and MDV is of possible pathogenetic importance in lymphomagenesis.…”

Section: Discussionmentioning

confidence: 99%

Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo

Torelli

Barozzi

Marasca

et al. 1995

Journal of Medical Virology

108

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Out of 64 cases of non-Hodgkin's lymphomas (NHL), 55 cases of Hodgkin's disease (HD) and 31 cases of multiple sclerosis (MS), 2 NHL, 7 HD and 1 MS cases were found positive by polymerase chain reaction (PCR) for the presence of HHV-6 sequences in pathologic lymph nodes of the lymphomas and in peripheral blood mononuclear cells (PBMCs) of MS. A further analysis of the PBMCs of the PCR positive cases by standard Southern blot technique revealed only 2 NHL, 3 HD and 1 MS cases as positive, indicating that these six patients have an unusually high viral copy number in the PBMCs. Restriction analysis, carried out using probes representative of different regions of the virus, showed that three cases retain only a deleted portion of the viral genome. In the remaining three cases a complete viral genome was present, containing the right end sequences in which the rep-like gene, possibly crucial to the viral and cellular life cycle, is located. The analysis by pulsed field gel electrophoresis (PFGE) of the total DNA of the PBMCs obtained directly, without culture from PBMCs of these last three cases (1 NHL, 1 HD, and 1 MS), using the same probes, showed the absence of free viral molecules and the association of viral sequences with high molecular weight DNA. These results are consistent with in vivo integration of the entire virus in the cellular genome. A further study of the same patients with chromosome fluorescence in situ hybridization (FISH) showed in all the three cases the presence of a specific hybridization site, located at the telomeric extremity of the short arm of chromosome 17 (17p13), suggesting that this location is at least a preferred site of an infrequent, but possibly biologically important, integration phenomenon.

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“…An interesting feature of the HHV-6 genome is that it contains reiterations of the hexanucleotide (GGGTTA) n near the ends of the DRs (199,274,316,508) (Fig. 2).…”

Section: Genomementioning

confidence: 99%

Human herpesvirus 6.

Braun

Dominguez

Pellett

1997

Clinical Microbiology Reviews

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A repeat sequence, GGGTTA, is shared by DNA of human herpesvirus 6 and Marek's disease virus

Cited by 73 publications

References 28 publications

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal Sites

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal Sites

Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo

Human herpesvirus 6.

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