Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2
Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2022.929053/full |
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| author | Angelica A. Palm Srinivas Veerla Jacob Lindman Per-Erik Isberg Emil Johansson Emil Johansson Antonio Biague Fredrik Månsson Hans Norrgren Joakim Esbjörnsson Patrik Medstrand Marianne Jansson |
| author_facet | Angelica A. Palm Srinivas Veerla Jacob Lindman Per-Erik Isberg Emil Johansson Emil Johansson Antonio Biague Fredrik Månsson Hans Norrgren Joakim Esbjörnsson Patrik Medstrand Marianne Jansson |
| author_sort | Angelica A. Palm |
| collection | DOAJ |
| description | Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-2. |
| first_indexed | 2024-12-12T05:45:13Z |
| format | Article |
| id | doaj.art-c17dd00b344445368c939f62e6871e73 |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-12-12T05:45:13Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-c17dd00b344445368c939f62e6871e732022-12-22T00:35:49ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-06-01210.3389/fviro.2022.929053929053Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2Angelica A. Palm0Srinivas Veerla1Jacob Lindman2Per-Erik Isberg3Emil Johansson4Emil Johansson5Antonio Biague6Fredrik Månsson7Hans Norrgren8Joakim Esbjörnsson9Patrik Medstrand10Marianne Jansson11Department of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Clinical Sciences Lund, Lund University, Lund, SwedenDepartment of Clinical Sciences Lund, Lund University, Lund, SwedenDepartment of Statistics, School of Economics and Management, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Translational Medicine, Lund University, Lund, SwedenThe National Laboratory of Public Health (LNSP), Bissau, Guinea-BissauDepartment of Translational Medicine, Lund University, Lund, SwedenDepartment of Clinical Sciences Lund, Lund University, Lund, SwedenDepartment of Translational Medicine, Lund University, Lund, SwedenDepartment of Translational Medicine, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDisease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-2.https://www.frontiersin.org/articles/10.3389/fviro.2022.929053/fullHIV-1HIV-2interferon-stimulated gene (ISG)viremiachronic infectiondisease severity |
| spellingShingle | Angelica A. Palm Srinivas Veerla Jacob Lindman Per-Erik Isberg Emil Johansson Emil Johansson Antonio Biague Fredrik Månsson Hans Norrgren Joakim Esbjörnsson Patrik Medstrand Marianne Jansson Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 Frontiers in Virology HIV-1 HIV-2 interferon-stimulated gene (ISG) viremia chronic infection disease severity |
| title | Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 |
| title_full | Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 |
| title_fullStr | Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 |
| title_full_unstemmed | Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 |
| title_short | Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2 |
| title_sort | interferon alpha inducible protein 27 expression is linked to disease severity in chronic infection of both hiv 1 and hiv 2 |
| topic | HIV-1 HIV-2 interferon-stimulated gene (ISG) viremia chronic infection disease severity |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2022.929053/full |
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