Reduced eIF3d accelerates HIV disease progression by attenuating CD8+ T cell function
| Autor: | Zining Zhang, Yongjun Jiang, Ying Pan, Hong Shang, Lin-Bo Yin, Yajing Fu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male T cell Eukaryotic Initiation Factor-3 Proliferation lcsh:Medicine Apoptosis HIV Infections Suppressor of Cytokine Signaling Proteins Biology CD8-Positive T-Lymphocytes CD8+ T cells Virus Replication Peripheral blood mononuclear cell Jurkat cells SOCS-7 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Interferon-gamma Jurkat Cells 0302 clinical medicine medicine Cytotoxic T cell Humans RNA Messenger IFN-γ Rapid progressors Cell Proliferation Gene knockdown Research lcsh:R HIV General Medicine 030104 developmental biology medicine.anatomical_structure Viral replication Gene Expression Regulation 030220 oncology & carcinogenesis eIF3d Cancer research Disease Progression Female CD8 |
| Zdroj: | Journal of Translational Medicine Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-13 (2019) |
| ISSN: | 1479-5876 |
| Popis: | Background In human immunodeficiency virus (HIV) infection, 10–15% of individuals exhibit a rapid decline in CD4+ T cells and become rapid progressors (RPs). Overall, understanding the factors affecting rapid disease progression in early HIV infection (EHI) can aid in treatment initiation. Recent studies show that eIF3s, classic scaffold proteins during the translation initiation process, can directly promote or inhibit the translation of mRNA, therefore participating in the regulation of cell function. However, to our knowledge, it has not been addressed whether eIF3s are involved in the diverse prognosis of HIV infection. Methods Expression of eIF3s in primary cells from early or chronic HIV-infected patients was detected by real-time PCR. To investigate the potential mechanisms of eIF3d in the regulation of CD8+ T cell function, complete transcriptomes of eIF3d-inhibited Jurkat T cells were sequenced by RNA sequencing (RNA-Seq). Additionally, to examine the effect of eIF3d on CD8+ T cell function, eIF3d expression was inhibited alone or in combination with SOCS-7 knockdown by siRNA in isolated CD8+ T cells. CD8+ T cell proliferation, IFN-r secretion and apoptosis were detected by flow cytometry. Moreover, the effect of eIF3d on HIV replication was evaluated in Jurkat cells, peripheral blood mononuclear cells (PBMCs) and CD4+ T cells with eIF3d knockdown using a pNL4-3 pseudotyped virus. Results At approximately 100 days of infection, only eIF3d was markedly decreased in RPs compared with chronic progressors (CPs). Expression of eIF3d correlated significantly with disease progression in EHI. Based on in vitro analyses, reduced eIF3d expression led to decreased proliferation and IFN-γ secretion and increased apoptosis in CD8+ T cells. Inhibited expression of eIF3d caused enhanced expression of SOCS-7, and inhibiting SOCS-7 expression by siRNA rescued the attenuated CD8+ T cell function caused by eIF3d. Finally, when eIF3d was inhibited in Jurkat cells, PBMCs and CD4+ T cells, pNL4-3-VSV-G virus replication was enhanced. Conclusions The current data highlight the importance of eIF3d in HIV infection by inhibiting CD8+ T cell function and promoting viral replication. Our study provides potential targets for improved immune intervention. Electronic supplementary material The online version of this article (10.1186/s12967-019-1925-0) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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