ipsvirus 发表于 2017-12-26 20:32:36

PLoS Pathog:人蛋白APOBEC3H或阻止SIV病毒传播到人类

根据一项新的研究,人体中的一种被称作APOBEC3H(A3H)的抗病毒蛋白可能抵抗在进化上产生HIV-1的猴免疫缺陷病毒黑猩猩毒株(chimpanzee strains of simian immunodeficiency virus, SIVcpz)的跨物种传播。2017年12月21日,德国杜塞尔多夫大学的Zeli Zhang和同事们将这一发现发表在PLoS Pathogens期刊上,论文标题为“Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans”。
http://cache1.bioon.com/webeditor/uploadfile/201712/20171226184110102.png
图片来自PLoS Pathogens, doi:10.1371/journal.ppat.1006746。

A3H是几种抑制慢病毒复制的被称作APOBEC3(A3)的抗病毒蛋白之一。HIV-1属于慢病毒。HIV-1起源自传播到人体中的SIVcpz。然而,很少有人探究人A3对SIVcpz的影响。

在这项新的研究中,Zhang和同事研究了黑猩猩和人类中的A3蛋白如何影响SIVcpz。他们在不同A3的存在下,让SIVcpz毒株感染一种实验室细胞系。基于一种新的方法,SIVcpz病毒经过基因修饰后在某些条件下发光,从而能够让研究人员定量确定它们在这些细胞中的传染性。

这些研究人员发现一种被称作A3H单体型II的人A3蛋白强烈地抑制SIVcpz。这是因为A3H抵抗SIVcpz产生的蛋白Vif,当然VIf也能够反击A3。A3H能够以不同的形式出现,除A3H单体型II之外的其他A3H形式也表现出类似的抵抗SIVcpz的活性。

利用来自大猩猩基因组计划(Great Ape Genome Project)的基因组测序数据,这些研究人员也发现人A3H具有比黑猩猩A3H更加多样性的形式。进一步的实验表明来自SIVcpz和大猩猩SIV的Vif蛋白能够降解黑猩猩A3H,但不能够降解A3H单体型II。

总体而言,这些发现提示着人类A3H可能阻止SIVcpz从黑猩猩传播到到人类。因此,进化上产生HIV-1的SIVcpz毒株的传播可能是从具有不稳定的A3H形式的人体中开始的。

(生物谷 Bioon.com)

ipsvirus 发表于 2017-12-26 20:33:20

Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans

Zeli Zhang, Qinyong Gu, Marc de Manuel Montero, Ignacio G. Bravo, Tomas Marques-Bonet, Dieter Häussinger, Carsten Münk

APOBEC3s (A3s) are potent restriction factors of human immunodeficiency virus type 1/simian immunodeficiency viruses (HIV-1/SIV), and can repress cross-species transmissions of lentiviruses. HIV-1 originated from a zoonotic infection of SIV of chimpanzee (SIVcpz) to humans. However, the impact of human A3s on the replication of SIVcpz remains unclear. By using novel SIVcpz reporter viruses, we identified that human APOBEC3B (A3B) and APOBEC3H (A3H) haplotype II strongly reduced the infectivity of SIVcpz, because both of them are resistant to SIVcpz Vifs. We further demonstrated that human A3H inhibited SIVcpz by deaminase dependent as well independent mechanisms. In addition, other stably expressed human A3H haplotypes and splice variants showed strong antiviral activity against SIVcpz. Moreover, most SIV and HIV lineage Vif proteins could degrade chimpanzee A3H, but no Vifs from SIVcpz and SIV of gorilla (SIVgor) lineages antagonized human A3H haplotype II. Expression of human A3H hapII in human T cells efficiently blocked the spreading replication of SIVcpz. The spreading replication of SIVcpz was also restricted by stable A3H in human PBMCs. Thus, we speculate that stably expressed human A3H protects humans against the cross-species transmission of SIVcpz and that SIVcpz spillover to humans may have started in individuals that harbor haplotypes of unstable A3H proteins.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006746
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