Dual roles for the telomeric repeats in chromosomally integrated human herpesvirus-6

Tamae Ohye; Hidehito Inagaki; Masaru Ihira; Yuki Higashimoto; Koji Kato; Junko Oikawa; Hiroshi Yagasaki; Takahiro Niizuma; Yoshiyuki Takahashi; Seiji Kojima; Tetsushi Yoshikawa; Hiroki Kurahashi

doi:10.1038/srep04559

Dual roles for the telomeric repeats in chromosomally integrated human herpesvirus-6

Tamae Ohye, Hidehito Inagaki, Masaru Ihira, Yuki Higashimoto, Koji Kato, Junko Oikawa, Hiroshi Yagasaki, Takahiro Niizuma, Yoshiyuki Takahashi, Seiji Kojima, Tetsushi Yoshikawa, Hiroki Kurahashi

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Abstract

Approximately 1 percent of healthy individuals carry human herpesvirus-6 within a host chromosome. This is referred to as chromosomally integrated herpesvirus-6 (CIHHV-6). In this study, we investigated the chromosomal integration site in six individuals harboring CIHHV-6B. Using FISH, we found that HHV-6B signals are consistently located at the telomeric region. The proximal endpoints of the integrated virus were mapped at one of two telomere-repeat-like sequences (TRSs) within the DR-R in all cases. In two cases, we isolated junction fragments between the viral TRS and human telomere repeats. The distal endpoints were mapped at the distal TRS in all cases. The size of the distal TRS was found to be ~5 kb which is sufficient to fulfill cellular telomeric functions. We conclude that the viral TRS in the DR regions fulfill dual functions for CIHHV-6: homology-mediated integration into the telomeric region of the chromosome and neo-telomere formation that is then stably transmitted.

Original language	English
Article number	4559
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep04559
Publication status	Published - 02-04-2014
Externally published	Yes

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title = "Dual roles for the telomeric repeats in chromosomally integrated human herpesvirus-6",

abstract = "Approximately 1 percent of healthy individuals carry human herpesvirus-6 within a host chromosome. This is referred to as chromosomally integrated herpesvirus-6 (CIHHV-6). In this study, we investigated the chromosomal integration site in six individuals harboring CIHHV-6B. Using FISH, we found that HHV-6B signals are consistently located at the telomeric region. The proximal endpoints of the integrated virus were mapped at one of two telomere-repeat-like sequences (TRSs) within the DR-R in all cases. In two cases, we isolated junction fragments between the viral TRS and human telomere repeats. The distal endpoints were mapped at the distal TRS in all cases. The size of the distal TRS was found to be ~5 kb which is sufficient to fulfill cellular telomeric functions. We conclude that the viral TRS in the DR regions fulfill dual functions for CIHHV-6: homology-mediated integration into the telomeric region of the chromosome and neo-telomere formation that is then stably transmitted.",

author = "Tamae Ohye and Hidehito Inagaki and Masaru Ihira and Yuki Higashimoto and Koji Kato and Junko Oikawa and Hiroshi Yagasaki and Takahiro Niizuma and Yoshiyuki Takahashi and Seiji Kojima and Tetsushi Yoshikawa and Hiroki Kurahashi",

note = "Funding Information: The authors thank Dr. Hiroshi Kogo and Makiko Tsutsumi for helpful discussions, Akiko Yoshikawa, Noriko Hayashizono and Narumi Kamiya for technical assistance. This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (24390085, 23659182, 23013019, http:// www.mext.go.jp), and from the Ministry of Health, Labour and Welfare of Japan, to H.K (10103465, http://www.mhlw.go.jp).",

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AU - Ohye, Tamae

AU - Inagaki, Hidehito

AU - Ihira, Masaru

AU - Higashimoto, Yuki

AU - Kato, Koji

AU - Oikawa, Junko

AU - Yagasaki, Hiroshi

AU - Niizuma, Takahiro

AU - Takahashi, Yoshiyuki

AU - Kojima, Seiji

AU - Yoshikawa, Tetsushi

AU - Kurahashi, Hiroki

N1 - Funding Information: The authors thank Dr. Hiroshi Kogo and Makiko Tsutsumi for helpful discussions, Akiko Yoshikawa, Noriko Hayashizono and Narumi Kamiya for technical assistance. This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (24390085, 23659182, 23013019, http:// www.mext.go.jp), and from the Ministry of Health, Labour and Welfare of Japan, to H.K (10103465, http://www.mhlw.go.jp).

PY - 2014/4/2

Y1 - 2014/4/2

N2 - Approximately 1 percent of healthy individuals carry human herpesvirus-6 within a host chromosome. This is referred to as chromosomally integrated herpesvirus-6 (CIHHV-6). In this study, we investigated the chromosomal integration site in six individuals harboring CIHHV-6B. Using FISH, we found that HHV-6B signals are consistently located at the telomeric region. The proximal endpoints of the integrated virus were mapped at one of two telomere-repeat-like sequences (TRSs) within the DR-R in all cases. In two cases, we isolated junction fragments between the viral TRS and human telomere repeats. The distal endpoints were mapped at the distal TRS in all cases. The size of the distal TRS was found to be ~5 kb which is sufficient to fulfill cellular telomeric functions. We conclude that the viral TRS in the DR regions fulfill dual functions for CIHHV-6: homology-mediated integration into the telomeric region of the chromosome and neo-telomere formation that is then stably transmitted.

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Dual roles for the telomeric repeats in chromosomally integrated human herpesvirus-6

Abstract

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