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Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner

Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of t...

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Autores principales: Imamichi, Tomozumi, Chen, Qian, Sowrirajan, Bharatwaj, Yang, Jun, Laverdure, Sylvain, Marquez, Mayra, Mele, Anthony R., Watkins, Catherine, Adelsberger, Joseph W., Higgins, Jeanette, Sui, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619827/
https://www.ncbi.nlm.nih.gov/pubmed/37910521
http://dx.doi.org/10.1371/journal.pone.0287829
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author Imamichi, Tomozumi
Chen, Qian
Sowrirajan, Bharatwaj
Yang, Jun
Laverdure, Sylvain
Marquez, Mayra
Mele, Anthony R.
Watkins, Catherine
Adelsberger, Joseph W.
Higgins, Jeanette
Sui, Hongyan
author_facet Imamichi, Tomozumi
Chen, Qian
Sowrirajan, Bharatwaj
Yang, Jun
Laverdure, Sylvain
Marquez, Mayra
Mele, Anthony R.
Watkins, Catherine
Adelsberger, Joseph W.
Higgins, Jeanette
Sui, Hongyan
author_sort Imamichi, Tomozumi
collection PubMed
description Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.
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spelling pubmed-106198272023-11-02 Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner Imamichi, Tomozumi Chen, Qian Sowrirajan, Bharatwaj Yang, Jun Laverdure, Sylvain Marquez, Mayra Mele, Anthony R. Watkins, Catherine Adelsberger, Joseph W. Higgins, Jeanette Sui, Hongyan PLoS One Research Article Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells. Public Library of Science 2023-11-01 /pmc/articles/PMC10619827/ /pubmed/37910521 http://dx.doi.org/10.1371/journal.pone.0287829 Text en © 2023 Imamichi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Imamichi, Tomozumi
Chen, Qian
Sowrirajan, Bharatwaj
Yang, Jun
Laverdure, Sylvain
Marquez, Mayra
Mele, Anthony R.
Watkins, Catherine
Adelsberger, Joseph W.
Higgins, Jeanette
Sui, Hongyan
Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title_full Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title_fullStr Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title_full_unstemmed Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title_short Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner
title_sort interleukin-27-induced hiv-resistant dendritic cells suppress reveres transcription following virus entry in an sptbn1, autophagy, and yb-1 independent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619827/
https://www.ncbi.nlm.nih.gov/pubmed/37910521
http://dx.doi.org/10.1371/journal.pone.0287829
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