The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach

Summary: The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infecte...

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Main Authors: Hiroo Katsuya, Saiful Islam, Benjy Jek Yang Tan, Jumpei Ito, Paola Miyazato, Misaki Matsuo, Yuki Inada, Saori C. Iwase, Yoshikazu Uchiyama, Hiroyuki Hata, Tomoo Sato, Naoko Yagishita, Natsumi Araya, Takaharu Ueno, Kisato Nosaka, Masahito Tokunaga, Makoto Yamagishi, Toshiki Watanabe, Kaoru Uchimaru, Jun-ichi Fujisawa, Atae Utsunomiya, Yoshihisa Yamano, Yorifumi Satou
Format: Article
Language:English
Published: Elsevier 2019-10-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719311933
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author Hiroo Katsuya
Saiful Islam
Benjy Jek Yang Tan
Jumpei Ito
Paola Miyazato
Misaki Matsuo
Yuki Inada
Saori C. Iwase
Yoshikazu Uchiyama
Hiroyuki Hata
Tomoo Sato
Naoko Yagishita
Natsumi Araya
Takaharu Ueno
Kisato Nosaka
Masahito Tokunaga
Makoto Yamagishi
Toshiki Watanabe
Kaoru Uchimaru
Jun-ichi Fujisawa
Atae Utsunomiya
Yoshihisa Yamano
Yorifumi Satou
spellingShingle Hiroo Katsuya
Saiful Islam
Benjy Jek Yang Tan
Jumpei Ito
Paola Miyazato
Misaki Matsuo
Yuki Inada
Saori C. Iwase
Yoshikazu Uchiyama
Hiroyuki Hata
Tomoo Sato
Naoko Yagishita
Natsumi Araya
Takaharu Ueno
Kisato Nosaka
Masahito Tokunaga
Makoto Yamagishi
Toshiki Watanabe
Kaoru Uchimaru
Jun-ichi Fujisawa
Atae Utsunomiya
Yoshihisa Yamano
Yorifumi Satou
The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
Cell Reports
author_facet Hiroo Katsuya
Saiful Islam
Benjy Jek Yang Tan
Jumpei Ito
Paola Miyazato
Misaki Matsuo
Yuki Inada
Saori C. Iwase
Yoshikazu Uchiyama
Hiroyuki Hata
Tomoo Sato
Naoko Yagishita
Natsumi Araya
Takaharu Ueno
Kisato Nosaka
Masahito Tokunaga
Makoto Yamagishi
Toshiki Watanabe
Kaoru Uchimaru
Jun-ichi Fujisawa
Atae Utsunomiya
Yoshihisa Yamano
Yorifumi Satou
author_sort Hiroo Katsuya
title The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
title_short The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
title_full The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
title_fullStr The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
title_full_unstemmed The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
title_sort nature of the htlv-1 provirus in naturally infected individuals analyzed by the viral dna-capture-seq approach
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2019-10-01
description Summary: The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that clones with defective-type proviruses exhibited a higher degree of clonal abundance than those with full-length proviruses. The frequency of defective-type proviruses in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate the robustness of viral DNA-capture-seq for HTLV-1 infection and suggest potential applications for other virus-associated cancers in humans. : Katsuya et al. demonstrate that HTLV-1 DNA-capture-seq provides comprehensive information, including the entire viral sequence, integration site, and clonal abundance of infected cells. Infected clones with defective-type proviruses are present in disease states and in asymptomatic carriers, and they proliferate more than full-length proviruses. Keywords: retrovirus, viral oncogenesis, HTLV-1, next-generation sequencing, DNA-capture-seq, viral integration site, clonality analysis, adult T cell leukemia-lymphoma, retroviral latency, HIV-1
url http://www.sciencedirect.com/science/article/pii/S2211124719311933
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spelling doaj-318a0d7e9d5a4845bb5c4617d8b725a52020-11-24T21:58:59ZengElsevierCell Reports2211-12472019-10-01293724735.e4The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq ApproachHiroo Katsuya0Saiful Islam1Benjy Jek Yang Tan2Jumpei Ito3Paola Miyazato4Misaki Matsuo5Yuki Inada6Saori C. Iwase7Yoshikazu Uchiyama8Hiroyuki Hata9Tomoo Sato10Naoko Yagishita11Natsumi Araya12Takaharu Ueno13Kisato Nosaka14Masahito Tokunaga15Makoto Yamagishi16Toshiki Watanabe17Kaoru Uchimaru18Jun-ichi Fujisawa19Atae Utsunomiya20Yoshihisa Yamano21Yorifumi Satou22Joint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanLaboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 606-8507 Kyoto, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanInternational Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, Japan; Division of Informative Clinical Sciences, Faculty of Medical Sciences, Kumamoto University, 860-0811 Kumamoto, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, JapanDepartment of Medical Physics, Faculty of Life Sciences, Kumamoto University, 860-0811 Kumamoto, JapanDivision of Informative Clinical Sciences, Faculty of Medical Sciences, Kumamoto University, 860-0811 Kumamoto, JapanDepartment of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, 211-0063 Kawasaki, JapanDepartment of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, 211-0063 Kawasaki, JapanDepartment of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, 211-0063 Kawasaki, JapanDepartment of Microbiology, Kansai Medical University, Hirakata, 573-1191 Osaka, JapanDepartment of Hematology, Rheumatology and Infectious Disease, Kumamoto University Hospital, 860-0811 Kumamoto, JapanDepartment of Hematology, Imamura General Hospital, 890-0064 Kagoshima, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8561 Tokyo, JapanThe Institute of Medical Science Research Hospital, The University of Tokyo, 108-8639 Tokyo, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8561 Tokyo, JapanDepartment of Microbiology, Kansai Medical University, Hirakata, 573-1191 Osaka, JapanDepartment of Hematology, Imamura General Hospital, 890-0064 Kagoshima, Japan; Graduate School of Medical and Dental Sciences, Kagoshima University, 890-8544 Kagoshima, JapanDepartment of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, 211-0063 Kawasaki, JapanJoint Research Center for Human Retrovirus Infection, Kumamoto University, 860-0811 Kumamoto, Japan; International Research Center for Medical Sciences (IRCMS), Kumamoto University, 860-0811 Kumamoto, Japan; Corresponding authorSummary: The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that clones with defective-type proviruses exhibited a higher degree of clonal abundance than those with full-length proviruses. The frequency of defective-type proviruses in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate the robustness of viral DNA-capture-seq for HTLV-1 infection and suggest potential applications for other virus-associated cancers in humans. : Katsuya et al. demonstrate that HTLV-1 DNA-capture-seq provides comprehensive information, including the entire viral sequence, integration site, and clonal abundance of infected cells. Infected clones with defective-type proviruses are present in disease states and in asymptomatic carriers, and they proliferate more than full-length proviruses. Keywords: retrovirus, viral oncogenesis, HTLV-1, next-generation sequencing, DNA-capture-seq, viral integration site, clonality analysis, adult T cell leukemia-lymphoma, retroviral latency, HIV-1http://www.sciencedirect.com/science/article/pii/S2211124719311933