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HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages

HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes fu...

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Autores principales: Martins, Laura J., Szaniawski, Matthew A., Williams, Elizabeth S. C. P., Coiras, Mayte, Hanley, Timothy M., Planelles, Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878269/
https://www.ncbi.nlm.nih.gov/pubmed/35215107
http://dx.doi.org/10.3390/pathogens11020163
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author Martins, Laura J.
Szaniawski, Matthew A.
Williams, Elizabeth S. C. P.
Coiras, Mayte
Hanley, Timothy M.
Planelles, Vicente
author_facet Martins, Laura J.
Szaniawski, Matthew A.
Williams, Elizabeth S. C. P.
Coiras, Mayte
Hanley, Timothy M.
Planelles, Vicente
author_sort Martins, Laura J.
collection PubMed
description HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes function to improve viral fitness by altering host pathways in ways that enable transmission to occur without interference from the immune response. We previously described changes in transcriptomes from HIV-1 infected and from IFN-stimulated macrophages and noted that transcription of IFN-regulated genes and genes related to cell cycle processes were upregulated during HIV-1 infection. In the present study, we sought to define the roles of individual viral accessory genes in upregulation of IFN-regulated and cell cycle-related genes using RNA sequencing. We observed that Vif induces a set of genes involved in mitotic processes and that these genes are potently downregulated upon stimulation with type-I and -II IFNs. Vpr also upregulated cell cycle-related genes and was largely responsible for inducing an attenuated IFN response. We note that the induced IFN response most closely resembled a type-III IFN response. Vpu and Nef-regulated smaller sets of genes whose transcriptomic signatures upon infection related to cytokine and chemokine processes. This work provides more insight regarding processes that are manipulated by HIV-1 accessory proteins at the transcriptional level.
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spelling pubmed-88782692022-02-26 HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages Martins, Laura J. Szaniawski, Matthew A. Williams, Elizabeth S. C. P. Coiras, Mayte Hanley, Timothy M. Planelles, Vicente Pathogens Article HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes function to improve viral fitness by altering host pathways in ways that enable transmission to occur without interference from the immune response. We previously described changes in transcriptomes from HIV-1 infected and from IFN-stimulated macrophages and noted that transcription of IFN-regulated genes and genes related to cell cycle processes were upregulated during HIV-1 infection. In the present study, we sought to define the roles of individual viral accessory genes in upregulation of IFN-regulated and cell cycle-related genes using RNA sequencing. We observed that Vif induces a set of genes involved in mitotic processes and that these genes are potently downregulated upon stimulation with type-I and -II IFNs. Vpr also upregulated cell cycle-related genes and was largely responsible for inducing an attenuated IFN response. We note that the induced IFN response most closely resembled a type-III IFN response. Vpu and Nef-regulated smaller sets of genes whose transcriptomic signatures upon infection related to cytokine and chemokine processes. This work provides more insight regarding processes that are manipulated by HIV-1 accessory proteins at the transcriptional level. MDPI 2022-01-26 /pmc/articles/PMC8878269/ /pubmed/35215107 http://dx.doi.org/10.3390/pathogens11020163 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martins, Laura J.
Szaniawski, Matthew A.
Williams, Elizabeth S. C. P.
Coiras, Mayte
Hanley, Timothy M.
Planelles, Vicente
HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title_full HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title_fullStr HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title_full_unstemmed HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title_short HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages
title_sort hiv-1 accessory proteins impart a modest interferon response and upregulate cell cycle-related genes in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878269/
https://www.ncbi.nlm.nih.gov/pubmed/35215107
http://dx.doi.org/10.3390/pathogens11020163
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