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HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains
The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged nuclear entry and transport of HIV-1 replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) and CD4(...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360574/ https://www.ncbi.nlm.nih.gov/pubmed/32665593 http://dx.doi.org/10.1038/s41467-020-17256-8 |
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author | Francis, Ashwanth C. Marin, Mariana Singh, Parmit K. Achuthan, Vasudevan Prellberg, Mathew J. Palermino-Rowland, Kristina Lan, Shuiyun Tedbury, Philip R. Sarafianos, Stefan G. Engelman, Alan N. Melikyan, Gregory B. |
author_facet | Francis, Ashwanth C. Marin, Mariana Singh, Parmit K. Achuthan, Vasudevan Prellberg, Mathew J. Palermino-Rowland, Kristina Lan, Shuiyun Tedbury, Philip R. Sarafianos, Stefan G. Engelman, Alan N. Melikyan, Gregory B. |
author_sort | Francis, Ashwanth C. |
collection | PubMed |
description | The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged nuclear entry and transport of HIV-1 replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) and CD4(+) T cells. We show that viral replication complexes traffic to and accumulate within nuclear speckles and that these steps precede the completion of viral DNA synthesis. HIV-1 transport to nuclear speckles is dependent on the interaction of the capsid proteins with host cleavage and polyadenylation specificity factor 6 (CPSF6), which is also required to stabilize the association of the viral replication complexes with nuclear speckles. Importantly, integration site analyses reveal a strong preference for HIV-1 to integrate into speckle-associated genomic domains. Collectively, our results demonstrate that nuclear speckles provide an architectural basis for nuclear homing of HIV-1 replication complexes and subsequent integration into associated genomic loci. |
format | Online Article Text |
id | pubmed-7360574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73605742020-07-20 HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains Francis, Ashwanth C. Marin, Mariana Singh, Parmit K. Achuthan, Vasudevan Prellberg, Mathew J. Palermino-Rowland, Kristina Lan, Shuiyun Tedbury, Philip R. Sarafianos, Stefan G. Engelman, Alan N. Melikyan, Gregory B. Nat Commun Article The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged nuclear entry and transport of HIV-1 replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) and CD4(+) T cells. We show that viral replication complexes traffic to and accumulate within nuclear speckles and that these steps precede the completion of viral DNA synthesis. HIV-1 transport to nuclear speckles is dependent on the interaction of the capsid proteins with host cleavage and polyadenylation specificity factor 6 (CPSF6), which is also required to stabilize the association of the viral replication complexes with nuclear speckles. Importantly, integration site analyses reveal a strong preference for HIV-1 to integrate into speckle-associated genomic domains. Collectively, our results demonstrate that nuclear speckles provide an architectural basis for nuclear homing of HIV-1 replication complexes and subsequent integration into associated genomic loci. Nature Publishing Group UK 2020-07-14 /pmc/articles/PMC7360574/ /pubmed/32665593 http://dx.doi.org/10.1038/s41467-020-17256-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Francis, Ashwanth C. Marin, Mariana Singh, Parmit K. Achuthan, Vasudevan Prellberg, Mathew J. Palermino-Rowland, Kristina Lan, Shuiyun Tedbury, Philip R. Sarafianos, Stefan G. Engelman, Alan N. Melikyan, Gregory B. HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title | HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title_full | HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title_fullStr | HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title_full_unstemmed | HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title_short | HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
title_sort | hiv-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360574/ https://www.ncbi.nlm.nih.gov/pubmed/32665593 http://dx.doi.org/10.1038/s41467-020-17256-8 |
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