Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection
Abstract Background Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-in...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-020-02252-9 |
| _version_ | 1819018576475979776 |
|---|---|
| author | Si-Yao Li Zi-Ning Zhang Yong‑Jun Jiang Ya‑Jing Fu Hong Shang |
| author_facet | Si-Yao Li Zi-Ning Zhang Yong‑Jun Jiang Ya‑Jing Fu Hong Shang |
| author_sort | Si-Yao Li |
| collection | DOAJ |
| description | Abstract Background Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-infection. Thus, understanding the similarities in the characteristics of CD8+ T cells in mono-HIV and HCV infection at the transcriptomic level contributes to the development of antiviral therapy. In this study, a meta-analysis of CD8+ T cell gene expression profiles derived from mono-HIV and HCV infected individuals at different stages of disease progression, was conducted to understand the common changes experienced by CD8+ T cells. Methods Five microarray datasets, reporting CD8+ T cell mRNA expression of the mono-HIV and HCV infected patients, were retrieved from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified via integrative meta-analysis of expression data (INMEX) program. Network analysis methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs. MirDIP and miRDB online prediction tools were used to predict potential microRNAs (miRNAs) targeting hub genes. Results First, we identified 625 and 154 DEGs in the CD8+ T cells originating from mono-HIV and HCV chronic progressor patients, respectively, compared to healthy individuals. Among them, interferon-stimulated genes (ISGs) including ISG15, IFIT3, ILI44L, CXCL8, FPR1 and TLR2, were upregulated after mono-HIV and HCV infection. Pathway enrichment analysis of DEGs showed that the “cytokine–cytokine receptor interaction” and “NF-kappa B” signaling pathways were upregulated after mono-HIV and HCV infection. In addition, we identified 92 and 50 DEGs in the CD8+ T cells of HIV non-progressor and HCV resolver patients, respectively, compared with corresponding chronic progressors. We observed attenuated mitosis and reduced ISG expression in HIV non-progressors and HCV resolvers compared with the corresponding chronic progressors. Finally, we identified miRNA-143-3p, predicted to target both IFIT3 in HIV and STAT5A in HCV infection. Conclusions We identified DEGs and transcriptional patterns in mono-HIV and HCV infected individuals at different stages of disease progression and identified miRNA-143-3p with potential to intervene disease progression, which provides a new strategy for developing targeted therapies. |
| first_indexed | 2024-12-21T03:21:37Z |
| format | Article |
| id | doaj.art-229ce4c61fcf4a698f9fa1f8b45398c9 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T03:21:37Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-229ce4c61fcf4a698f9fa1f8b45398c92022-12-21T19:17:40ZengBMCJournal of Translational Medicine1479-58762020-02-0118111110.1186/s12967-020-02252-9Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infectionSi-Yao Li0Zi-Ning Zhang1Yong‑Jun Jiang2Ya‑Jing Fu3Hong Shang4NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityNHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityNHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityNHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityNHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityAbstract Background Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-infection. Thus, understanding the similarities in the characteristics of CD8+ T cells in mono-HIV and HCV infection at the transcriptomic level contributes to the development of antiviral therapy. In this study, a meta-analysis of CD8+ T cell gene expression profiles derived from mono-HIV and HCV infected individuals at different stages of disease progression, was conducted to understand the common changes experienced by CD8+ T cells. Methods Five microarray datasets, reporting CD8+ T cell mRNA expression of the mono-HIV and HCV infected patients, were retrieved from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified via integrative meta-analysis of expression data (INMEX) program. Network analysis methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs. MirDIP and miRDB online prediction tools were used to predict potential microRNAs (miRNAs) targeting hub genes. Results First, we identified 625 and 154 DEGs in the CD8+ T cells originating from mono-HIV and HCV chronic progressor patients, respectively, compared to healthy individuals. Among them, interferon-stimulated genes (ISGs) including ISG15, IFIT3, ILI44L, CXCL8, FPR1 and TLR2, were upregulated after mono-HIV and HCV infection. Pathway enrichment analysis of DEGs showed that the “cytokine–cytokine receptor interaction” and “NF-kappa B” signaling pathways were upregulated after mono-HIV and HCV infection. In addition, we identified 92 and 50 DEGs in the CD8+ T cells of HIV non-progressor and HCV resolver patients, respectively, compared with corresponding chronic progressors. We observed attenuated mitosis and reduced ISG expression in HIV non-progressors and HCV resolvers compared with the corresponding chronic progressors. Finally, we identified miRNA-143-3p, predicted to target both IFIT3 in HIV and STAT5A in HCV infection. Conclusions We identified DEGs and transcriptional patterns in mono-HIV and HCV infected individuals at different stages of disease progression and identified miRNA-143-3p with potential to intervene disease progression, which provides a new strategy for developing targeted therapies.http://link.springer.com/article/10.1186/s12967-020-02252-9HIVHCVCD8+ T cellsLong-term non-progressorsResolversMicroarray |
| spellingShingle | Si-Yao Li Zi-Ning Zhang Yong‑Jun Jiang Ya‑Jing Fu Hong Shang Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection Journal of Translational Medicine HIV HCV CD8+ T cells Long-term non-progressors Resolvers Microarray |
| title | Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection |
| title_full | Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection |
| title_fullStr | Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection |
| title_full_unstemmed | Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection |
| title_short | Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection |
| title_sort | transcriptional insights into the cd8 t cell response in mono hiv and hcv infection |
| topic | HIV HCV CD8+ T cells Long-term non-progressors Resolvers Microarray |
| url | http://link.springer.com/article/10.1186/s12967-020-02252-9 |
| work_keys_str_mv | AT siyaoli transcriptionalinsightsintothecd8tcellresponseinmonohivandhcvinfection AT ziningzhang transcriptionalinsightsintothecd8tcellresponseinmonohivandhcvinfection AT yongjunjiang transcriptionalinsightsintothecd8tcellresponseinmonohivandhcvinfection AT yajingfu transcriptionalinsightsintothecd8tcellresponseinmonohivandhcvinfection AT hongshang transcriptionalinsightsintothecd8tcellresponseinmonohivandhcvinfection |