Pr-957, a selective immunoproteasome inhibitor, reactivates latent hiv-1 through p-tefb activation mediated by hsf-1
文献类型：期刊论文
| 作者 | Lin, Jian1; Zhang, Xuanxuan1; Lu, Wanzhen1; Xu, Xinfeng1; Pan, Xiaoyan1,2; Liang, Taizhen1; Duan, Siqin1; Chen, Yi1; Li, Lin1; Liu, Shuwen1,3 |
| 刊名 | Biochemical pharmacology
 |
| 出版日期 | 2018-10-01 |
| 卷号 | 156页码:511-523 |
| ISSN号 | 0006-2952 |
| 关键词 | Hiv-1 latency Lras Pr-957 P-tefb Heat shock factor 1 |
| DOI | 10.1016/j.bcp.2018.08.042 |
| 通讯作者 | Liu, shuwen(liusw@smu.edu.cn) |
| 英文摘要 | The existence of latent reservoirs of human immunodeficiency virus type-1 (hiv-1) is a major obstacle in eliminating the virus. thus, an urgent need exists for effective latency reversing agents (lras) based on the "shock and kill" strategy. proteasome inhibitors were recently studied as lras, but were considered too toxic for clinical use. here, we demonstrated that pr-957, a selective immunoproteasome inhibitor, effectively reactivated latent hiv-1 provirus in vitro and ex vivo. our data also suggests that pr-957 has relatively low cytotoxicity. furthermore, it does not influence global t cell activation and decreases the expression levels of hiv-1 receptors/co-receptors. we demonstrated synergistic activation of latent hiv-1 with pr-957 and prostratin (a protein kinase c activator) that alleviated the extent of t cell activation induced by prostratin. in addition, pr 957 exhibited latency reversing efficacy through activating p-tefb mediated by hsf-1 pathway. moreover, pr 957 did not affect the activity of combination antiretroviral therapy (cart) drugs and the pr-957-reactivated virus was effectively inhibited with cart drugs. in conclusion, the immunoproteasome inhibitor pr-957 is a promising candidate lra for future hiv-1 eradication strategies. |
| WOS关键词 | CD4(+) T-CELLS ; ANTIRETROVIRAL THERAPY ; COMBINATION THERAPY ; SUBUNIT LMP7 ; INFECTION ; SHOCK ; VORINOSTAT ; EXPRESSION ; RESISTANCE ; INTEGRASE |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000448491500049 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373228 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Liu, Shuwen |
| 作者单位 | 1.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 3.Southern Med Univ, Guangdong Prov Inst Nephrol, State Key Lab Organ Failure Res, Guangzhou 510515, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Jian,Zhang, Xuanxuan,Lu, Wanzhen,et al. Pr-957, a selective immunoproteasome inhibitor, reactivates latent hiv-1 through p-tefb activation mediated by hsf-1[J]. Biochemical pharmacology,2018,156:511-523. |
| APA | Lin, Jian.,Zhang, Xuanxuan.,Lu, Wanzhen.,Xu, Xinfeng.,Pan, Xiaoyan.,...&Liu, Shuwen.(2018).Pr-957, a selective immunoproteasome inhibitor, reactivates latent hiv-1 through p-tefb activation mediated by hsf-1.Biochemical pharmacology,156,511-523. |
| MLA | Lin, Jian,et al."Pr-957, a selective immunoproteasome inhibitor, reactivates latent hiv-1 through p-tefb activation mediated by hsf-1".Biochemical pharmacology 156(2018):511-523. |
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来源：武汉病毒研究所
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