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《第十二届全国免疫学学术大会摘要汇编》2017年
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Transcriptome Analysis Reveal that the Violent Interferon Response and Impaired Immune Control Accelerates SIV Disease Progression of Aged Chinese Rhesus Macaques

Zheng Hong-Yi  Shao Yong  Chen Min  Wang Xue-Hui  Pang Wei  Wu Dong-Dong  Zheng Yong-Tang  
【摘要】:Background Despite successful viral suppression by anti-retroviral therapy(ART),elderly HIV~+ patients still have a slower rate of immune reconstitution and a higher risk of mortality and AIDS progression than adult patients.However,the underlying reasons still not fully tested.Objective:We constructed the aged Chinese rhesus macaque(ChRM) AIDS models to find the characteristics and explore the mechanisms of elderly AIDS.Methods We intensively compared the immunological,virological and transcriptome dynamics between 6 young(mean age = 7) and 12 old(mean age =18) ChRM throughout the 1 year of SIVmac239 infection.Results After 42 days post infection,5 old ChRM gradually died of AIDS complications.Old ChRM showed a faster AIDS development than young macaques as their rapidly elevated plasma viral load,fast loss of CD4~+ T cells and serious inversion of CD4/CD8 ratio.We further profiled the transcriptome of PBMC samples from d0,d10,d30,d90 and d360 days post infection.Consistent with the phenotypic results,SIV infection triggered a dramatical upregulation of genes linked to interferon signaling and viral RNA transcription and replication in both young and old groups.However,young macaques showed a specific downregulation of some gene sets involved in immune activation,like JNK-MAPK,cytokine(IL-1,IL-12,IL-22 and IL-23) and p53 signaling pathway.While the CD28 and TCR signaling pathway and the negative regulation of apoptosis and immune system progress are reduced especially in old group.Analysis of differential expression genes revealed that old macaques display a stronger activation of genes involved in virus response and defense and young macaques have a special ability to relieve the activation of lymphocytes and protein kinase.Conclusion Overall,we demonstrated that the rapid disease progression of elderly HV patients may be induced by uncontrollable immune response,especially type Ⅰ interferon response.

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