Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins.
Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins.
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DOI：
10.1128/mbio.01985-16
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发表时间：
2016-11-22
期刊：
影响因子：
6.4
通讯作者：
Rein A
中科院分区：
文献类型：
--
作者：
Ahi YS;Zhang S;Thappeta Y;Denman A;Feizpour A;Gummuluru S;Reinhard B;Muriaux D;Fivash MJ;Rein A
γ逆转录病毒，如鼠白血病病毒（MLV），除了将形成子代病毒颗粒的典型Gag、Pol和Env蛋白外，还编码称为“glycogag”（糖基化Gag）的蛋白。MLV glycogag含有整个Gag序列加上88个残基的N-末端延伸。最近有报道称，glycogag与HIV-1的Nef蛋白一样，抵消了细胞蛋白Serinc 5的抗病毒作用。我们已经发现，与先前的工作一致，glycogag强烈增强了MLV与某些Env蛋白的感染性，但对其他蛋白则没有。然而，相比之下，glycogag对携带埃博拉病毒糖蛋白的MLV是有害的。Glycogag在病毒感染性方面可以被马传染性贫血病毒的无关S2蛋白所取代。我们设计了一种用于病毒进入的测定，其中病毒颗粒将Cre重组酶递送到细胞中，导致报告基因的表达。该试验的数据表明，glycogag和S2对MLV感染性的阳性和阴性影响均在病毒进入水平发挥。此外，用Serinc 5表达质粒转染产病毒细胞降低了携带异嗜性MLV Env的MLV的感染性和进入能力，特别是在不存在glycogag的情况下。相反，Serinc 5表达消除了glycogag对携带埃博拉病毒糖蛋白的MLV的感染性和进入能力的负面影响。由于Serinc 5可能影响细胞磷脂代谢，因此似乎所有这些对病毒进入的影响都可能来自病毒膜脂质组成的变化。许多小鼠白血病病毒（MLV）编码一种称为“glycogag”的蛋白质。glycogag的功能尚未完全了解，但在某些情况下，它可以在缺乏HIV-1蛋白Nef的情况下帮助HIV-1复制。反过来，Nef抵消细胞蛋白Serinc 5。Glycogag可增强部分但非全部MLV Env蛋白（在与细胞表面受体结合后介导病毒进入宿主细胞）对MLV的感染性。我们现在报告说，glycogag的行为，通过增强病毒的进入，像Nef，glycogag拮抗丝氨酸5。令人惊讶的是，glycogag和Serinc 5对携带埃博拉病毒糖蛋白的MLV颗粒的进入和感染性的影响与用MLV Env蛋白观察到的相反。马传染性贫血病毒（EIAV）的S2蛋白在我们的实验中与glycogag功能相似。因此，三种逆转录病毒（HIV-1，MLV和EIAV）已经独立进化出了对抗Serinc 5的辅助蛋白。
Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called “glycogag” (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others. In contrast, however, glycogag was detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced, with respect to viral infectivity, by the unrelated S2 protein of equine infectious anemia virus. We devised an assay for viral entry in which virus particles deliver the Cre recombinase into cells, leading to the expression of a reporter. Data from this assay showed that both the positive and the negative effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus entry. Moreover, transfection of the virus-producing cells with a Serinc5 expression plasmid reduced the infectivity and entry capability of MLV carrying xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5 expression abrogated the negative effects of glycogag upon the infectivity and entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may influence cellular phospholipid metabolism, it seems possible that all of these effects on virus entry derive from changes in the lipid composition of viral membranes. Many murine leukemia viruses (MLVs) encode a protein called “glycogag.” The function of glycogag is not fully understood, but it can assist HIV-1 replication in the absence of the HIV-1 protein Nef under some circumstances. In turn, Nef counteracts the cellular protein Serinc5. Glycogag enhances the infectivity of MLVs with some but not all MLV Env proteins (which mediate viral entry into the host cell upon binding to cell surface receptors). We now report that glycogag acts by enhancing viral entry and that, like Nef, glycogag antagonizes Serinc5. Surprisingly, the effects of glycogag and Serinc5 upon the entry and infectivity of MLV particles carrying an Ebolavirus glycoprotein are the opposite of those observed with the MLV Env proteins. The unrelated S2 protein of equine infectious anemia virus (EIAV) is functionally analogous to glycogag in our experiments. Thus, three retroviruses (HIV-1, MLV, and EIAV) have independently evolved accessory proteins that counteract Serinc5.
影响因子：
3.3
作者：
Oliveira NM;Trikha R;McKnight Á
通讯作者：
McKnight Á