IDO1, FAT10, IFI6, and GILT Are Involved in the Antiretroviral Activity of γ-Interferon and IDO1 Restricts Retrovirus Infection by Autophagy Enhancement

Kubo, Yasuo; Yasui, Kiyoshi; Izumida, Mai; Hayashi, Hideki; Matsuyama, Tomohiro

doi:10.3390/cells11142240

Cited by 7 publications

(2 citation statements)

References 48 publications

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“…IFIT3 inhibits the translation of viral proteins [ 91 ]. IFI6 induces autophagy cell-type dependent and inhibits HIV [ 92 , 93 ]. Therefore, the anti-HIV effects of the six genes were not related with HIV RT reaction; they were excluded from the potential host factors.…”

Section: Resultsmentioning

confidence: 99%

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

Imamichi,

Chen,

Sowrirajan

et al. 2023

PLoS ONE

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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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Section: Resultsmentioning

confidence: 99%

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

Imamichi,

Chen,

Sowrirajan

et al. 2023

PLoS ONE

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show abstract

“…induces autophagy cell-type dependent and inhibits HIV [92,93]. Therefore, the anti-HIV effects of the six genes were not related with HIV RT reaction; they were excluded from the potential host factors.…”

Section: Plos Onementioning

confidence: 99%

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

Imamichi¹,

Chen²,

Sowrirajan³

et al. 2023

Preprint

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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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Sociobehavioral Risk Factors and Clinical Implications of Late Presentation Among People Living with HIV in the Brazilian Amazon Region

Pereira,

França,

Costa

et al. 2024

AIDS Behav

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This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7–12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-ɣ, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

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IDO1, FAT10, IFI6, and GILT Are Involved in the Antiretroviral Activity of γ-Interferon and IDO1 Restricts Retrovirus Infection by Autophagy Enhancement

Cited by 7 publications

References 48 publications

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

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

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

Sociobehavioral Risk Factors and Clinical Implications of Late Presentation Among People Living with HIV in the Brazilian Amazon Region

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