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HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle

N(6)-methyladenosine (m(6)A) is the most abundant HIV RNA modification but the interplay between the m(6)A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction facto...

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Autores principales: Jurczyszak, Denise, Zhang, Wen, Terry, Sandra N., Kehrer, Thomas, Bermúdez González, Maria C., McGregor, Emma, Mulder, Lubbertus C. F., Eckwahl, Matthew J., Pan, Tao, Simon, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043784/
https://www.ncbi.nlm.nih.gov/pubmed/32053707
http://dx.doi.org/10.1371/journal.ppat.1008305
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author Jurczyszak, Denise
Zhang, Wen
Terry, Sandra N.
Kehrer, Thomas
Bermúdez González, Maria C.
McGregor, Emma
Mulder, Lubbertus C. F.
Eckwahl, Matthew J.
Pan, Tao
Simon, Viviana
author_facet Jurczyszak, Denise
Zhang, Wen
Terry, Sandra N.
Kehrer, Thomas
Bermúdez González, Maria C.
McGregor, Emma
Mulder, Lubbertus C. F.
Eckwahl, Matthew J.
Pan, Tao
Simon, Viviana
author_sort Jurczyszak, Denise
collection PubMed
description N(6)-methyladenosine (m(6)A) is the most abundant HIV RNA modification but the interplay between the m(6)A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m(6)A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m(6)A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion.
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spelling pubmed-70437842020-03-09 HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle Jurczyszak, Denise Zhang, Wen Terry, Sandra N. Kehrer, Thomas Bermúdez González, Maria C. McGregor, Emma Mulder, Lubbertus C. F. Eckwahl, Matthew J. Pan, Tao Simon, Viviana PLoS Pathog Research Article N(6)-methyladenosine (m(6)A) is the most abundant HIV RNA modification but the interplay between the m(6)A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m(6)A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m(6)A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion. Public Library of Science 2020-02-13 /pmc/articles/PMC7043784/ /pubmed/32053707 http://dx.doi.org/10.1371/journal.ppat.1008305 Text en © 2020 Jurczyszak et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jurczyszak, Denise
Zhang, Wen
Terry, Sandra N.
Kehrer, Thomas
Bermúdez González, Maria C.
McGregor, Emma
Mulder, Lubbertus C. F.
Eckwahl, Matthew J.
Pan, Tao
Simon, Viviana
HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title_full HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title_fullStr HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title_full_unstemmed HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title_short HIV protease cleaves the antiviral m(6)A reader protein YTHDF3 in the viral particle
title_sort hiv protease cleaves the antiviral m(6)a reader protein ythdf3 in the viral particle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043784/
https://www.ncbi.nlm.nih.gov/pubmed/32053707
http://dx.doi.org/10.1371/journal.ppat.1008305
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