Mechanism of cell-to-cell infection with gamma herpesviruses through B-cell

• Project/Area Number: 15K08509
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Katano Harutaka 国立感染症研究所, 感染病理部, 室長 (70321867)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ウイルス / KSHV / 細胞間感染 / EBV / エクソソーム / マイクロRNA / ガンマヘルペスウイルス

Outline of Final Research Achievements

Molecular mechanism of cell-to-cell infection was investigated in EBV and KSHV infection. Next generation sequencer revealed profiles of microRNA expression in EBV or KSHV infected cells and diseases. Exo-motif which induced miRNA to exosome was identified in sequences of KSHV and EBV miRNAs. Cell-to cell contact of KSHV-infected cell with non-infected cells induced expression of RTA, an immediate early protein of KSHV. Function of KSHV-encoded vIL-6 was also analyzed on plasmablastic cells with IL-6-dependent growth.

Academic Significance and Societal Importance of the Research Achievements

ヒトガンマヘルペスウイルスであるEBVや KSHV（HHV-8)はヒトB細胞に潜伏感染し、その後、上皮(EBV)や血管内皮(KSHV)に感染し、それぞれ、癌やカポジ肉腫などの悪性腫瘍を発症する。細胞間感染はヘルペスウイルスの疾患の成立に重要と考えられ、その分子機構を解明することは、ヘルペスウイルス属に共通の感染機構が見いだせる可能性がある.　感染細胞におけるウイルス由来のマイクロRNAが大量発現していることに関しては、感染におけるmiRNAが何らかの役割を果たしていることが推察され、新規治療法の標的となりうることを示す。

Research Products

• [Journal Article] Pathological Features of Kaposi’s Sarcoma-Associated Herpesvirus Infection (2018)
  • Author(s): Katano Harutaka
  • Journal Title: Adv Exp Med Biol Volume: 1045 Pages: 357-376
  • DOI: 10.1007/978-981-10-7230-7_16
  • ISBN: 9789811072291, 9789811072307
  • Peer Reviewed
• [Journal Article] Expression and Function of Kaposi’s Sarcoma-Associated Herpesvirus Non-coding RNAs (2018)
  • Author(s): Katano Harutaka
  • Journal Title: Current Clinical Microbiology Reports Volume: 5 Issue: 4 Pages: 211-218
  • DOI: 10.1007/s40588-018-0101-2
  • Peer Reviewed
• [Journal Article] Infection of Epstein?Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines (2018)
  • Author(s): Nanbo Asuka、Katano Harutaka、Kataoka Michiyo、Hoshina Shiho、Sekizuka Tsuyoshi、Kuroda Makoto、Ohba Yusuke
  • Journal Title: Cancers Volume: 10 Issue: 7 Pages: 237-237
  • DOI: 10.3390/cancers10070237
  • NAID: 120006491456
  • Peer Reviewed / Open Access
• [Journal Article] Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets (2017)
  • Author(s): Mine Sohtaro、Hishima Tsunekazu、Suganuma Akihiko、Fukumoto Hitomi、Sato Yuko、Kataoka Michiyo、Sekizuka Tsuyoshi、Kuroda Makoto、Suzuki Tadaki、Hasegawa Hideki、Fukayama Masashi、Katano Harutaka
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 10188-10188
  • DOI: 10.1038/s41598-017-10684-5
  • Peer Reviewed / Open Access
• [Journal Article] Conserved sequences of BART and BHRF regions encoding viral microRNAs in Epstein-Barr virus-associated lymphoma (2017)
  • Author(s): Sunagawa Keishin、Hishima Tsunekazu、Fukumoto Hitomi、Hasegawa Hideki、Katano Harutaka
  • Journal Title: BMC Research Notes Volume: 10 Issue: 1 Pages: 279-279
  • DOI: 10.1186/s13104-017-2603-z
  • Peer Reviewed / Open Access
• [Journal Article] Next-generation sequencing of miRNAs in clinical samples of Epstein-Barr virus-associated B-cell lymphomas (2017)
  • Author(s): Sakamoto K, Sekizuka T, Uehara T, Hishima T, Mine S, Fukumoto H, Sato Y, Hasegawa H, Kuroda M, Katano H
  • Journal Title: Cancer Med Volume: 6 Issue: 3 Pages: 605-618
  • DOI: 10.1002/cam4.1006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Profile of Exosomal and Intracellular microRNA in Gamma-Herpesvirus-Infected Lymphoma Cell Lines (2016)
  • Author(s): Hoshina S, Sekizuka T, Kataoka M, Hasegawa H, Hamada H, Kuroda M, Katano H
  • Journal Title: PLoS One Volume: 11 Issue: 9 Pages: e0162574-e0162574
  • DOI: 10.1371/journal.pone.0162574
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishing and characterizing a new primary effusion lymphoma cell line harboring Kaposi's sarcoma-associated herpesvirus (2016)
  • Author(s): Osawa M, Mine S, Ota S, Kato K, Sekizuka T, Kuroda M, Kataoka M, Fukumoto H, Sato Y, Kanno T, Hasegawa H, Ueda K, Fukayama M, Maeda T, Kanoh S, Kawana A, Fujikura Y, Katano H
  • Journal Title: Infect Agent Cancer Volume: 11 Issue: 1 Pages: 37-37
  • DOI: 10.1186/s13027-016-0086-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fumagillin, a potent angiogenesis inhibitor, induces Kaposi sarcoma-associated herpesvirus replication in primary effusion lymphoma cells (2015)
  • Author(s): Kanno T, Uehara T, Osawa M, Fukumoto H, Mine S, Ueda K, Hasegawa H, Katano H
  • Journal Title: Biochem Biophys Res Commun Volume: 463 Issue: 4 Pages: 1267-72
  • DOI: 10.1016/j.bbrc.2015.06.100
  • Peer Reviewed / Acknowledgement Compliant