Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1
Abstract Background In the absence of antiretroviral treatments (ARTs), a small group of individuals infected with HIV, including long-term non-progressors (LTNPs) who maintain high levels of CD4+ T cells for more than 7–10 years in the absence of ART and in particular a subgroup of LTNPs, elite con...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12920-018-0443-x |
| _version_ | 1818608143149563904 |
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| author | Sun Young Lee Yong Kwang Park Cheol-Hee Yoon Kisoon Kim Kyung-Chang Kim |
| author_facet | Sun Young Lee Yong Kwang Park Cheol-Hee Yoon Kisoon Kim Kyung-Chang Kim |
| author_sort | Sun Young Lee |
| collection | DOAJ |
| description | Abstract Background In the absence of antiretroviral treatments (ARTs), a small group of individuals infected with HIV, including long-term non-progressors (LTNPs) who maintain high levels of CD4+ T cells for more than 7–10 years in the absence of ART and in particular a subgroup of LTNPs, elite controllers (ECs), who have low levels of viremia, remain clinically and/or immunologically stable for years. However, the mechanism of stable disease progression in LTNPs and ECs needs to be elucidated to help those infected with HIV-1 remain healthy. In this study, to identify the characteristics of gene expression profiles and biomarkers in LTNPs, we performed a meta-analysis using multiple gene expression profiles among LTNPs, individuals infected with HIV-1 without ART, individuals infected with HIV-1 with ART, and healthy controls. Methods The gene expression profiles obtained from the Gene Expression Omnibus (GEO) microarray data repositories were classified into three groups: LTNPs versus healthy controls (first group, 3 studies), LTNPs versus patients infected with HIV-1 without ART (second group, 3 studies), and LTNPs versus patients infected with HIV-1 with ART (third group, 3 studies). In addition, we considered a fourth group, patients infected with HIV-1 without ART versus healthy controls (3 studies), to exclude genes associated with HIV-1 infection in the three groups. For each group, we performed a meta-analysis using the RankProd method to identify and compare the differentially expressed genes (DEGs) in the three groups. Results We identified the 14 common DEGs in the three groups when comparing them with each other. Most belonged to immune responses, antigen processing and presentation, the interferon-gamma-mediated signaling pathway, and T cell co-stimulation. Of these DEGs, PHLDA1 was up-regulated and ACTB and ACTG1 were down-regulated in all three groups. However, the rest of the up- or down-regulated genes were discordant in the three groups. Additionally, ACTB and ACTG1 are known to inhibit viral assembly and production, and THBS1 is known to inhibit HIV-1 infection. Conclusions These results suggest that significant genes identified in a meta-analysis provide clues to the cause of delayed disease progression and give a deeper understanding of HIV pathogenesis in LTNPs. |
| first_indexed | 2024-12-16T14:37:57Z |
| format | Article |
| id | doaj.art-052b125feda1433e862e3817c69da75f |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-16T14:37:57Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-052b125feda1433e862e3817c69da75f2022-12-21T22:28:03ZengBMCBMC Medical Genomics1755-87942019-01-0112111010.1186/s12920-018-0443-xMeta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1Sun Young Lee0Yong Kwang Park1Cheol-Hee Yoon2Kisoon Kim3Kyung-Chang Kim4Division of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of HealthDivision of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of HealthDivision of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of HealthDivision of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of HealthDivision of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of HealthAbstract Background In the absence of antiretroviral treatments (ARTs), a small group of individuals infected with HIV, including long-term non-progressors (LTNPs) who maintain high levels of CD4+ T cells for more than 7–10 years in the absence of ART and in particular a subgroup of LTNPs, elite controllers (ECs), who have low levels of viremia, remain clinically and/or immunologically stable for years. However, the mechanism of stable disease progression in LTNPs and ECs needs to be elucidated to help those infected with HIV-1 remain healthy. In this study, to identify the characteristics of gene expression profiles and biomarkers in LTNPs, we performed a meta-analysis using multiple gene expression profiles among LTNPs, individuals infected with HIV-1 without ART, individuals infected with HIV-1 with ART, and healthy controls. Methods The gene expression profiles obtained from the Gene Expression Omnibus (GEO) microarray data repositories were classified into three groups: LTNPs versus healthy controls (first group, 3 studies), LTNPs versus patients infected with HIV-1 without ART (second group, 3 studies), and LTNPs versus patients infected with HIV-1 with ART (third group, 3 studies). In addition, we considered a fourth group, patients infected with HIV-1 without ART versus healthy controls (3 studies), to exclude genes associated with HIV-1 infection in the three groups. For each group, we performed a meta-analysis using the RankProd method to identify and compare the differentially expressed genes (DEGs) in the three groups. Results We identified the 14 common DEGs in the three groups when comparing them with each other. Most belonged to immune responses, antigen processing and presentation, the interferon-gamma-mediated signaling pathway, and T cell co-stimulation. Of these DEGs, PHLDA1 was up-regulated and ACTB and ACTG1 were down-regulated in all three groups. However, the rest of the up- or down-regulated genes were discordant in the three groups. Additionally, ACTB and ACTG1 are known to inhibit viral assembly and production, and THBS1 is known to inhibit HIV-1 infection. Conclusions These results suggest that significant genes identified in a meta-analysis provide clues to the cause of delayed disease progression and give a deeper understanding of HIV pathogenesis in LTNPs.http://link.springer.com/article/10.1186/s12920-018-0443-xHIV-1Long-term non-progressorsGene expression profileBiomarkersMeta-analysis |
| spellingShingle | Sun Young Lee Yong Kwang Park Cheol-Hee Yoon Kisoon Kim Kyung-Chang Kim Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 BMC Medical Genomics HIV-1 Long-term non-progressors Gene expression profile Biomarkers Meta-analysis |
| title | Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 |
| title_full | Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 |
| title_fullStr | Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 |
| title_full_unstemmed | Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 |
| title_short | Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1 |
| title_sort | meta analysis of gene expression profiles in long term non progressors infected with hiv 1 |
| topic | HIV-1 Long-term non-progressors Gene expression profile Biomarkers Meta-analysis |
| url | http://link.springer.com/article/10.1186/s12920-018-0443-x |
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