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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287829&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850160082136858624 |
|---|---|
| author | Tomozumi Imamichi Qian Chen Bharatwaj Sowrirajan Jun Yang Sylvain Laverdure Mayra Marquez Anthony R Mele Catherine Watkins Joseph W Adelsberger Jeanette Higgins Hongyan Sui |
| author_facet | Tomozumi Imamichi Qian Chen Bharatwaj Sowrirajan Jun Yang Sylvain Laverdure Mayra Marquez Anthony R Mele Catherine Watkins Joseph W Adelsberger Jeanette Higgins Hongyan Sui |
| author_sort | Tomozumi Imamichi |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-d9cd4b97cfd44cb98cdd2b63fd2aacb2 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d9cd4b97cfd44cb98cdd2b63fd2aacb22025-08-20T02:23:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011811e028782910.1371/journal.pone.0287829Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.Tomozumi ImamichiQian ChenBharatwaj SowrirajanJun YangSylvain LaverdureMayra MarquezAnthony R MeleCatherine WatkinsJoseph W AdelsbergerJeanette HigginsHongyan SuiInterleukin (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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287829&type=printable |
| spellingShingle | Tomozumi Imamichi Qian Chen Bharatwaj Sowrirajan Jun Yang Sylvain Laverdure Mayra Marquez Anthony R Mele Catherine Watkins Joseph W Adelsberger Jeanette Higgins Hongyan Sui Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287829&type=printable |
| work_keys_str_mv | AT tomozumiimamichi interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT qianchen interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT bharatwajsowrirajan interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT junyang interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT sylvainlaverdure interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT mayramarquez interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT anthonyrmele interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT catherinewatkins interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT josephwadelsberger interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT jeanettehiggins interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner AT hongyansui interleukin27inducedhivresistantdendriticcellssuppressreverestranscriptionfollowingvirusentryinansptbn1autophagyandyb1independentmanner |