Para acceder a los documentos con el texto completo, por favor, siga el siguiente enlace: http://hdl.handle.net/10230/34837

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
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.
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).
-HIV
-Viral antisense RNA
-Latency
-Reactivation
-Latency reversing agents
© 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.
http://creativecommons.org/licenses/by/4.0/
Artículo
Artículo - Versión publicada
Frontiers
         

Mostrar el registro completo del ítem

Documentos relacionados

Otros documentos del mismo autor/a

Tsunetsugu-Yokota, Yasuko; Kobayashi-Ishihara, Mie; Wada, Yamato; Terahara, Kazutaka; Takeyama, Haruko; Kawana-Tachikawa, Ai; Tokunaga, Kenzo; Yamagishi, Makoto; Martínez Vesga, Javier Pablo; Meyerhans, Andreas
Chen, Heng-Chang; Martínez Vesga, Javier Pablo; Zorita, Eduard; Meyerhans, Andreas; Filion, Guillaume
Carreras Sureda, Amado, 1986-; Rubio Moscardó, Fanny; Olvera, Alex; Argilaguet, Jordi; Kiefer, Kerstin, 1986-; Mothe, Beatriz; Meyerhans, Andreas; Brander, Christian; Vicente García, Rubén, 1978-
Olvera, Alex; Martínez, Javier P.; Casadellà, Maria; Llano, Anuska; Rosás, Míriam; Mothe, Beatriz; Ruiz Riol, Marta; Arsequell, Gemma; Valencia, Gregorio; Noguera Julián, Marc; Paredes, Roger; Meyerhans, Andreas; Brander, Christian
Berger, Christoph T.; Llano, Anuska; Carlson, Jonathan M.; Brumme, Zabrina L.; Brockman, Mark A.; Cedeño, Samandhy; Harrigan, R.; Kaufmann, Daniel E.; Heckerman, David; Meyerhans, Andreas; Brander, Christian