干扰素
生物
蛋白酶体
基因
病毒学
病毒复制
免疫系统
衣壳
病毒
细胞生物学
遗传学
作者
Jose M. Jiménez-Guardeño,Luis Apolonia,Gilberto Betancor,Michael H. Malim
出处
期刊:Nature microbiology
日期:2019-03-18
卷期号:4 (6): 933-940
被引量:56
标识
DOI:10.1038/s41564-019-0402-0
摘要
Type 1 interferon suppresses viral replication by upregulating the expression of interferon-stimulated genes with diverse antiviral properties1. The replication of human immunodeficiency virus type 1 (HIV-1) is naturally inhibited by interferon, with the steps between viral entry and chromosomal integration of viral DNA being notably susceptible2-5. The interferon-stimulated gene myxovirus resistance 2 has been defined as an effective postentry inhibitor of HIV-1, but is only partially responsible for interferon's suppressive effect6-8. Using small interfering RNA-based library screening in interferon-α-treated cells, we sought to characterize further interferon-stimulated genes that target the pre-integration phases of HIV-1 infection, and identified human tripartite-containing motif 5α (TRIM5α) as a potent anti-HIV-1 restriction factor. Human TRIM5α, in contrast with many nonhuman orthologues, has not generally been ascribed substantial HIV-1 inhibitory function, a finding attributed to ineffective recognition of cytoplasmic viral capsids by TRIM5α2,9,10. Here, we demonstrate that interferon-α-mediated stimulation of the immunoproteasome, a proteasome isoform mainly present in immune cells and distinguished from the constitutive proteasome by virtue of its different catalytic β-subunits, as well as the proteasome activator 28 regulatory complex11-13, and the associated accelerated turnover of TRIM5α underpin the reprogramming of human TRIM5α for effective capsid-dependent inhibition of HIV-1 DNA synthesis and infection. These observations identify a mechanism for regulating human TRIM5α antiviral function in human cells and rationalize how TRIM5α participates in the immune control of HIV-1 infection.
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