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| Status |
Public on Dec 15, 2020 |
| Title |
Genome-wide DNA methylation analysis reveals dynamic changes in metabolic and immune-regulatory pathways during uncontrolled SIV infection |
| Platform organism |
Homo sapiens |
| Sample organisms |
Macaca mulatta; Chlorocebus sabaeus |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
The molecular mechanisms underlying HIV-induced inflammation remain incompletely defined although they associate with morbidity and progression to AIDS. Here we used non-human primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infection in respectively macaques and African green monkeys. We longitudinally analyzed DNA methylation changes in CD4+ T cells from lymph node and blood using species-compatible probes on human 450K methylation BeadArrays. Selected identified sites were validated using bisulfite-pyrosequencing of an independent cohort of uninfected, viremic and SIV controller macaques. Tissue- and species-specific DNA methylation changes were observed after SIV infection. The most affected genes in pathogenic SIV infection were related to metabolic pathways and Th1 signaling. SIV-infected macaques displayed increased insulin sensitivity early in the chronic phase of infection, which correlated with T cell activation. Moreover, DNA methylation changes in the Th1 pathway were associated with altered gene expression. Out of the 11 selected genes for validation, six genes showed differential methylation in viremic and uninfected macaques. In contrast, no significant differences were found between uninfected and SIV-controller macaques. In summary, pathogenic SIV infection associates with DNA methylation changes in genes related to metabolism and immune-regulation.
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| Overall design |
Genome-wide changes in DNA methylation in CD4+ T cells isolated from lymphnodes and blood were analyzed longitudinally in the 5 AGM (O7199, O7249, SV081, SV082 and SV084) and 4 MAC (53482, 54189, 54410 and 85696). DNA methylation was measured at three timepoints for MAC: before infection, during acute (day 14 p.i.) and during early chronic infection (day 62-65 p.i.). For AGM, we measured changes in DNA methylation in CD4+ T cells at the same three time points in LN and at two time points in blood (before infection and early chronic infection, as not enough material was available during acute infection). In addition, pre-infection and chronic infection samples (up to day+1787 p.i. for AGM and +850 p.i. for MAC) from another fourteen AGM (06003-3, A7737, A8533, B2338, SV092, SV071, SV072, SV073, SV074, SV075, SV104, SV1101, SV1102, SV1103) and twelve MAC (9801046, 9808282, 9813552, VI219, 503052, 503068, 504034, 98R0016, 98R0078, O90528, 81998, 90874) were also analyzed to increase sample size. The genome-wide analysis was performed using Infinium HumanMethylation450K BeadChip (Illumina) restricting the analysis to a subset of probes that target CpGs at a unique location on the MAC and AGM genomes composed of 171,912 probes for AGM and 168,466 probes for MAC.
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| Contributor(s) |
Jochems SP, Jacquelin B, Busato F, Pichon F, Müller-Trutwin M, Tost J |
| Citation(s) |
33298174 |
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| Submission date |
Jan 15, 2020 |
| Last update date |
Dec 15, 2020 |
| Contact name |
Jorg Tost |
| E-mail(s) |
jorgtost@gmail.com
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| Phone |
0033160878423
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| Organization name |
CEA-Institut de Genomique, Centre National de Genotypage
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| Lab |
Laboratory for Epigenetics & Environment
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| Street address |
2 rue Gaston Cremieux
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| City |
Evry |
| ZIP/Postal code |
91000 |
| Country |
France |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (77)
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| GSM4272931 |
MAC_54410_Pre, lymph node |
| GSM4272932 |
MAC_85696_Pre, lymph node |
| GSM4272933 |
MAC_85696_D65, lymph node |
| GSM4272934 |
MAC_53482_D14, lymph node |
| GSM4272935 |
MAC_53482_D65, lymph node |
| GSM4272936 |
MAC_54189_D14, lymph node |
| GSM4272937 |
MAC_54410_D14, lymph node |
| GSM4272938 |
MAC_54410_D65, lymph node |
| GSM4272939 |
MAC_85696_D14, Blood (85696_D14) |
| GSM4272940 |
MAC_53482_Pre, Blood |
| GSM4272941 |
MAC_53482_D65, Blood |
| GSM4272942 |
MAC_54189_D14, Blood |
| GSM4272943 |
MAC_54189_D62, Blood |
| GSM4272944 |
MAC_54410_D14, Blood |
| GSM4272945 |
MAC_54410_D65, Blood |
| GSM4272946 |
MAC_85696_Pre, Blood |
| GSM4272947 |
MAC_85696_D14, Blood (RM85696-J14) |
| GSM4272948 |
MAC_85696_D63, Blood |
| GSM4272949 |
MAC_9801046_Euth, lymph node |
| GSM4272950 |
MAC_9808282_Euth, lymph node |
| GSM4272951 |
MAC_9813552_Euth, lymph node |
| GSM4272952 |
MAC_VI219_Euth, lymph node |
| GSM4272953 |
MAC_503052_Chr, lymph node |
| GSM4272954 |
MAC_503068_Chr, lymph node |
| GSM4272955 |
MAC_504034_Chr, lymph node |
| GSM4272956 |
MAC_98R0016_Chr, lymph node |
| GSM4272957 |
MAC_98R0078_Chr, lymph node |
| GSM4272958 |
MAC_O90528_Pre, lymph node |
| GSM4272959 |
MAC_81998_Pre, Blood |
| GSM4272960 |
MAC_90874_Pre, Blood |
| GSM4272961 |
MAC_503052_Chr, Blood |
| GSM4272962 |
MAC_503068_Chr, Blood |
| GSM4272963 |
MAC_504034_Chr, Blood |
| GSM4272964 |
MAC_54189_Pre, Blood |
| GSM4272965 |
MAC_54410_Pre, Blood |
| GSM4272966 |
MAC_98R0016_Chr, Blood |
| GSM4272967 |
MAC_98R0078_Chr, Blood |
| GSM4272968 |
MAC_O90528_Pre, Blood |
| GSM4272969 |
MAC_VI219_Chr, Blood |
| GSM4272970 |
AGM_O7199_Pre, lymph node |
| GSM4272971 |
AGM_O7249_Pre, lymph node |
| GSM4272972 |
AGM_SV081_D14, lymph node |
| GSM4272973 |
AGM_SV082_Pre, lymph node |
| GSM4272974 |
AGM_SV084_Pre, lymph node |
| GSM4272975 |
AGM_O7199_D14, lymph node |
| GSM4272976 |
AGM_O7249_D14, lymph node |
| GSM4272977 |
AGM_O7249_D65, lymph node |
| GSM4272978 |
AGM_SV081_D65, lymph node |
| GSM4272979 |
AGM_SV082_D14, lymph node |
| GSM4272980 |
AGM_SV082_D65, lymph node |
| GSM4272981 |
AGM_SV084_D65, lymph node |
| GSM4272982 |
AGM_06003-3_Pre, lymph node |
| GSM4272983 |
AGM_O7249_Pre, Blood |
| GSM4272984 |
AGM_O7249_D64, Blood |
| GSM4272985 |
AGM_A7737_Euth, lymph node |
| GSM4272986 |
AGM_A8533_Euth, lymph node |
| GSM4272987 |
AGM_B2338_Euth, lymph node |
| GSM4272988 |
AGM_SV084_Pre, Blood |
| GSM4272989 |
AGM_SV084_D64, Blood |
| GSM4272990 |
AGM_AGM SV092_Pre, Blood |
| GSM4272991 |
AGM_AGM SV092_Chr, Blood |
| GSM4272992 |
AGM_O7199_Pre, Blood |
| GSM4272993 |
AGM_O7199_Chr, Blood |
| GSM4272994 |
AGM_SV071_Pre, Blood |
| GSM4272995 |
AGM_SV072_Chr, Blood |
| GSM4272996 |
AGM_SV073_Chr, Blood |
| GSM4272997 |
AGM_SV074_Chr, Blood |
| GSM4272998 |
AGM_SV075_Pre, Blood |
| GSM4272999 |
AGM_SV082_Pre, Blood |
| GSM4273000 |
AGM_SV104_Chr, Blood |
| GSM4273001 |
AGM_SV1101_Pre, Blood |
| GSM4273002 |
AGM_SV1102_Pre, Blood |
| GSM4273003 |
AGM_SV1103_Pre, Blood |
| GSM4273004 |
AGM_SV1103_Pre, Blood |
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| Relations |
| BioProject |
PRJNA601421 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143708_Detection.Pval.csv.gz |
2.7 Mb |
(ftp)(http) |
CSV |
| GSE143708_Matrix_signal_intensities.csv.gz |
141.1 Mb |
(ftp)(http) |
CSV |
| GSE143708_RAW.tar |
781.6 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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