Nature同时发布3篇实验性文章介绍HIV1新靶点
table]UCSF大学利用AP-MS技术筛选18种HIV1蛋白与HEK293、Jurkat细胞系蛋白的相互作用。另一篇文章，介绍人转录因子CBF-β与HIV的Vif在感染过程中共同引起DNA脱氨酶APOBEC3G降解。 吉大一院与JHSPH的研究者也独立发现Vif-CBF-β 可能是一个非常重要的HIV靶点。
In their primary paper, titled “Global landscape of HIV–human protein complexes,” the UCSF researchers, led by Nevan J. Krogan, Ph.D., identified 497 HIV–human protein interactions involving 435 separate human proteins. Forty percent of these interactions were identified in both the HEK293 and Jurkat cell lines, and many of the host proteins hijacked by HIV were highly conserved across primates.
When the team analyzed the functional categories of host proteins associated with each HIV protein, they found an enrichment of host factors involved in transcription physically linked to the HIV transcription factor Tat. There was in addition an enrichment of host proteins thought to be involved in the regulation of ubiquitination associating with Vpu, Vpr, and Vif, which are HIV accessory factors that hijack ubiquitin ligases. One notable finding was that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3, and one of 11 host proteins identified that acts to inhibit HIV replication.
The UCSF’s analyses also identified a physical interaction between the HIV accessory protein, Vif, and the transcription cofactor CBF-β, as part of its hijacking of a ubiquitin ligase complex that targets APOBEC3G for degradation. Additional RNA knockdown and genetic complementation studies reported in the team’s second paper indicate that CBF-β is required for Vif-mediated degradation of APOBEC3G, and for preserving HIV-1 infectivity. In this paper, titled “Vif hijacks CBF-b to degrade APOBEC3G and promote HIV-1 infection,” the UCSF team concludes that “methods of disrupting the CBF-β–Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.”
This latter work is supported by the Jilin University and Johns Hopkins team, led by Xiao-Fang Yu, Ph.D. Dr. Yu et al report on independent studies demonstrating that CBF-b is a key regulator of HIV-1 Vif function. Their work, including CBF-β knockdown studies, showed that CBF-β is critical for Vif-induced endogenous APOBEC3G degradation and HIV-1 replication in H9 CD4+ T cells. While the results indicated that CGF-β isn’t required for the interaction between Vif and APOBEC3G, it was essential for assembly of the Vif ubiquitin-ligase complex. “Considering the importance of the interaction between Vif and CBF-b, disrupting this interaction represents an attractive pharmacological intervention against HIV-1,” they conclude. The investigators report their findings in a paper titled “T-cell differentiation factor CBF-b regulates HIV-1 Vif-mediated evasion of host restriction.”
谢在第一时间转来这样重要的资料。辛苦了。对流感疫情不能有麻痹的思想。基础学科的研究很重要。
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