An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers
Abstract Background Despite that most HIV-infected individuals experience progressive CD4+ T cell loss and develop AIDS, a minority of HIV-infected individuals remain asymptomatic and maintain high level CD4+ T cell counts several years after seroconversion. Efforts have been made to understand the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1777-7 |
| _version_ | 1811296107108499456 |
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| author | Jiwei Ding Ling Ma Jianyuan Zhao Yongli Xie Jinming Zhou Xiaoyu Li Shan Cen |
| author_facet | Jiwei Ding Ling Ma Jianyuan Zhao Yongli Xie Jinming Zhou Xiaoyu Li Shan Cen |
| author_sort | Jiwei Ding |
| collection | DOAJ |
| description | Abstract Background Despite that most HIV-infected individuals experience progressive CD4+ T cell loss and develop AIDS, a minority of HIV-infected individuals remain asymptomatic and maintain high level CD4+ T cell counts several years after seroconversion. Efforts have been made to understand the determinants of the nonprogressive status, exemplified by the clinical course of elite controllers (ECs) who maintain an undetectable viremia and viremic nonprogressors (VNPs) who have a normal CD4+ count in spite of circulating viral load. However, the intrinsic mechanism underlying nonprogression remained elusive. In this study, we performed an integrative analysis of transcriptional profiles to pinpoint the underlying mechanism for a naturally occurring viral control. Methods Three microarray datasets, reporting mRNA expression of the LTNPs or ECs in HIV-infected patients, were retrieved from Gene Expression Ominbus (GEO) or Arrayexpress databases. These datasets, profiled on the same type of microarray chip, were selected and merged by a bioinformatic approach to build a meta-analysis derived transcriptome (MADNT). In addition, we investigated the different transcriptional pathways and potential biomarkers in CD4+ and CD8+ cells in ECs and whole blood in VNPs compared to HIV progressors. The combined transcriptome and each subgroup was subject to gene set enrichment analysis and weighted co-expression network analysis to search potential transcription patterns related to the non-progressive status. Results 30 up-regulated genes and 83 down-regulated genes were identified in lymphocytes from integrative meta-analysis of expression data. The interferon response and innate immune activation was reduced in both CD4+ and CD8+ T cells from ECs. Several characteristic genes including CMPK1, CBX7, EIF3L, EIF4A and ZNF395 were indicated to be highly correlated with viremic control. Besides that, we indicated that the reduction of ribosome components and blockade of translation facilitated AIDS disease progression. Most interestingly, among VNPs who have a relatively high viral load, we detected a two gene-interaction networks which showed a strong correlation to immune control even with a rigorous statistical threshold (p value = 2−e4 and p value = 0.004, respectively) by WGCNA. Conclusions We have identified differentially expressed genes and transcriptional patterns in ECs and VNPs compared to normal chronic HIV-infected individuals. Our study provides new insights into the pathogenesis of HIV and AIDS and clues for the therapeutic strategies for anti-retroviral administration. |
| first_indexed | 2024-04-13T05:43:27Z |
| format | Article |
| id | doaj.art-d7e0436165314b2cb737d203496c856a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T05:43:27Z |
| publishDate | 2019-01-01 |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-d7e0436165314b2cb737d203496c856a2022-12-22T03:00:02ZengBMCJournal of Translational Medicine1479-58762019-01-0117111310.1186/s12967-019-1777-7An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllersJiwei Ding0Ling Ma1Jianyuan Zhao2Yongli Xie3Jinming Zhou4Xiaoyu Li5Shan Cen6Institute of Medicinal Biotechnology, Chinese Academy of Medical SciencesInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesKey Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal UniversityInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesAbstract Background Despite that most HIV-infected individuals experience progressive CD4+ T cell loss and develop AIDS, a minority of HIV-infected individuals remain asymptomatic and maintain high level CD4+ T cell counts several years after seroconversion. Efforts have been made to understand the determinants of the nonprogressive status, exemplified by the clinical course of elite controllers (ECs) who maintain an undetectable viremia and viremic nonprogressors (VNPs) who have a normal CD4+ count in spite of circulating viral load. However, the intrinsic mechanism underlying nonprogression remained elusive. In this study, we performed an integrative analysis of transcriptional profiles to pinpoint the underlying mechanism for a naturally occurring viral control. Methods Three microarray datasets, reporting mRNA expression of the LTNPs or ECs in HIV-infected patients, were retrieved from Gene Expression Ominbus (GEO) or Arrayexpress databases. These datasets, profiled on the same type of microarray chip, were selected and merged by a bioinformatic approach to build a meta-analysis derived transcriptome (MADNT). In addition, we investigated the different transcriptional pathways and potential biomarkers in CD4+ and CD8+ cells in ECs and whole blood in VNPs compared to HIV progressors. The combined transcriptome and each subgroup was subject to gene set enrichment analysis and weighted co-expression network analysis to search potential transcription patterns related to the non-progressive status. Results 30 up-regulated genes and 83 down-regulated genes were identified in lymphocytes from integrative meta-analysis of expression data. The interferon response and innate immune activation was reduced in both CD4+ and CD8+ T cells from ECs. Several characteristic genes including CMPK1, CBX7, EIF3L, EIF4A and ZNF395 were indicated to be highly correlated with viremic control. Besides that, we indicated that the reduction of ribosome components and blockade of translation facilitated AIDS disease progression. Most interestingly, among VNPs who have a relatively high viral load, we detected a two gene-interaction networks which showed a strong correlation to immune control even with a rigorous statistical threshold (p value = 2−e4 and p value = 0.004, respectively) by WGCNA. Conclusions We have identified differentially expressed genes and transcriptional patterns in ECs and VNPs compared to normal chronic HIV-infected individuals. Our study provides new insights into the pathogenesis of HIV and AIDS and clues for the therapeutic strategies for anti-retroviral administration.http://link.springer.com/article/10.1186/s12967-019-1777-7Elite controllerLong-term nonprogressorViremic nonprogressorMeta-analysisGSEAWGCNA |
| spellingShingle | Jiwei Ding Ling Ma Jianyuan Zhao Yongli Xie Jinming Zhou Xiaoyu Li Shan Cen An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers Journal of Translational Medicine Elite controller Long-term nonprogressor Viremic nonprogressor Meta-analysis GSEA WGCNA |
| title | An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers |
| title_full | An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers |
| title_fullStr | An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers |
| title_full_unstemmed | An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers |
| title_short | An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers |
| title_sort | integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in hiv infected long term non progressors and elite controllers |
| topic | Elite controller Long-term nonprogressor Viremic nonprogressor Meta-analysis GSEA WGCNA |
| url | http://link.springer.com/article/10.1186/s12967-019-1777-7 |
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