Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads
Sex differences play a role in the pathogenesis of a number of viral diseases. In HIV-1, several studies have reported that chronically infected women have significantly lower plasma viremia than men, although the exact mechanism by which this occurs has yet to be identified. We have performed bulk...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507530/full |
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| author | Elina El-Badry Luxiao Chen Khader Ghneim Ziyi Li Kelsie Brooks Jake Rhodes Rafick Sekaly William Kilembe Susan Allen Susan Allen Susan Allen Hao Wu Eric Hunter Eric Hunter |
| author_facet | Elina El-Badry Luxiao Chen Khader Ghneim Ziyi Li Kelsie Brooks Jake Rhodes Rafick Sekaly William Kilembe Susan Allen Susan Allen Susan Allen Hao Wu Eric Hunter Eric Hunter |
| author_sort | Elina El-Badry |
| collection | DOAJ |
| description | Sex differences play a role in the pathogenesis of a number of viral diseases. In HIV-1, several studies have reported that chronically infected women have significantly lower plasma viremia than men, although the exact mechanism by which this occurs has yet to be identified. We have performed bulk RNA-seq experiments comparing gene expression between CD4+ T cells from acutely HIV-1–infected men and women in Zambia, because we observe lower viral load (VL) despite higher CD4+ T-cell activation in these women during acute/early infection. In a univariate analysis, we have identified a number of differentially expressed genes in naïve, central memory, and effector memory CD4 T cells of women with consistent elevated expression of genes linked to type 1 interferon (IFN) signaling. Moreover, after controlling for differences in VL and CD4+ T-cell count, genes within the type I IFN signaling pathway were further shown to be more highly expressed in women, whereas those genes more highly expressed in men showed no such enrichment. A subset of the genes highly expressed in women was further identified, including several involved in type I IFN signaling in response to viral infections (IRF7, DDX58, SAMHD1, OAS2, and TRIM14), that both are more highly expressed in CD4+ T cells from women and negatively correlated with VL, suggesting that they play a role in the comparative control of VL observed in women. |
| format | Article |
| id | doaj-art-10e8f4b09d7141c7b8f36fb0b49e294f |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-10e8f4b09d7141c7b8f36fb0b49e294f2025-01-20T05:23:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15075301507530Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loadsElina El-Badry0Luxiao Chen1Khader Ghneim2Ziyi Li3Kelsie Brooks4Jake Rhodes5Rafick Sekaly6William Kilembe7Susan Allen8Susan Allen9Susan Allen10Hao Wu11Eric Hunter12Eric Hunter13Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesEmory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United StatesEmory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesCenter for Family Health in Zambia, Lusaka, ZambiaEmory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesCenter for Family Health in Zambia, Lusaka, ZambiaDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesEmory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesSex differences play a role in the pathogenesis of a number of viral diseases. In HIV-1, several studies have reported that chronically infected women have significantly lower plasma viremia than men, although the exact mechanism by which this occurs has yet to be identified. We have performed bulk RNA-seq experiments comparing gene expression between CD4+ T cells from acutely HIV-1–infected men and women in Zambia, because we observe lower viral load (VL) despite higher CD4+ T-cell activation in these women during acute/early infection. In a univariate analysis, we have identified a number of differentially expressed genes in naïve, central memory, and effector memory CD4 T cells of women with consistent elevated expression of genes linked to type 1 interferon (IFN) signaling. Moreover, after controlling for differences in VL and CD4+ T-cell count, genes within the type I IFN signaling pathway were further shown to be more highly expressed in women, whereas those genes more highly expressed in men showed no such enrichment. A subset of the genes highly expressed in women was further identified, including several involved in type I IFN signaling in response to viral infections (IRF7, DDX58, SAMHD1, OAS2, and TRIM14), that both are more highly expressed in CD4+ T cells from women and negatively correlated with VL, suggesting that they play a role in the comparative control of VL observed in women.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507530/fullHIVsex-based differencesinterferonacute infectiontranscriptomics |
| spellingShingle | Elina El-Badry Luxiao Chen Khader Ghneim Ziyi Li Kelsie Brooks Jake Rhodes Rafick Sekaly William Kilembe Susan Allen Susan Allen Susan Allen Hao Wu Eric Hunter Eric Hunter Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads Frontiers in Immunology HIV sex-based differences interferon acute infection transcriptomics |
| title | Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads |
| title_full | Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads |
| title_fullStr | Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads |
| title_full_unstemmed | Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads |
| title_short | Heightened expression of type I interferon signaling genes in CD4+ T cells from acutely HIV-1–infected women is associated with lower viral loads |
| title_sort | heightened expression of type i interferon signaling genes in cd4 t cells from acutely hiv 1 infected women is associated with lower viral loads |
| topic | HIV sex-based differences interferon acute infection transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507530/full |
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