HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency

Kobayashi-Ishihara, Mie; Terahara, Kazutaka; Martínez Vesga, Javier Pablo; Yamagishi, Makoto; Iwabuchi, Ryutaro; Brander, Christian; Ato, Manabu; Watanabe, Toshiki; Meyerhans, Andreas; Tsunetsugu-Yokota, Yasuko

HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency

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dc.contributor.author Kobayashi-Ishihara, Mieca
dc.contributor.author Terahara, Kazutakaca
dc.contributor.author Martínez Vesga, Javier Pabloca
dc.contributor.author Yamagishi, Makotoca
dc.contributor.author Iwabuchi, Ryutaroca
dc.contributor.author Brander, Christianca
dc.contributor.author Ato, Manabuca
dc.contributor.author Watanabe, Toshikica
dc.contributor.author Meyerhans, Andreasca
dc.contributor.author Tsunetsugu-Yokota, Yasukoca
dc.date.accessioned 2018-06-06T07:45:53Z
dc.date.available 2018-06-06T07:45:53Z
dc.date.issued 2018
dc.description.abstract Latently infected T lymphocytes are an important barrier toward eliminating a persistent HIV infection. Here we describe an HIV-based recombinant fluorescent-lentivirus referred to as “rfl-HIV” that enables to analyze sense and antisense transcription by means of fluorescence reporter genes. This model virus exhibited similar transcriptional and functional properties of the antisense transcript as observed with a wild type HIV, and largely facilitated the generation of latently-infected T cells clones. We show that latently-infected cells can be divided into two types, those with and those without antisense transcription. Upon addition of latency reversal agents, only the cells that lack antisense transcripts are readily reactivated to transcribe HIV. Thus, antisense transcripts may exhibit a dominant suppressor activity and can lock an integrated provirus into a non-reactivatable state. These findings could have important implications for the development of strategies to eradicate HIV from infected individuals.
dc.description.sponsorship This work was supported by grants from Japan Society for the Promotion of Science (JSPS KAKENHI #15H06877 for MK-I, #JP17K08800 for KT), ViiV Healthcare Japan Research Grant 2015 (MK-I), Grants-in-Aid from the Ministry of Health, Labour and Welfare (H24-AIDS-008 to YT-Y) and Japan Agency for Medical Research and Development (AMED #JP17fk0410305h0103 to YT-Y and #JP18fk0410003 to KT). MK-I received Fellowships from Japan Foundation for AIDS Prevention and JSPS Oversea Research Fellow Program. AM and JM were supported by a grant from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER grant no. SAF2016-75505-R (AEI/MINEICO/FEDER, UE) and through the “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0370).
dc.format.mimetype application/pdf
dc.identifier.citation Kobayashi-Ishihara M, Terahara K, Martinez JP, Yamagishi M, Iwabuchi R, Brander C et al. HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency. Front Microbiol. 2018 May;9:1066. DOI: 10.3389/fmicb.2018.01066
dc.identifier.doi http://dx.doi.org/10.3389/fmicb.2018.01066
dc.identifier.issn 1664-302X
dc.identifier.uri http://hdl.handle.net/10230/34837
dc.language.iso eng
dc.publisher Frontiersca
dc.relation.ispartof Frontiers in Microbiology. 2018 May;9:1066
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75505-R
dc.rights © 2018 Kobayashi-Ishihara, Terahara, Martinez, Yamagishi, Iwabuchi, Brander, Ato, Watanabe, Meyerhans and Tsunetsugu-Yokota. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword HIV
dc.subject.keyword Viral antisense RNA
dc.subject.keyword Latency
dc.subject.keyword Reactivation
dc.subject.keyword Latency reversing agents
dc.title HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latencyca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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