Human and murine APOBEC3s restrict replication of koala retrovirus by different mechanisms.
Human and murine APOBEC3s restrict replication of koala retrovirus by different mechanisms.
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DOI：
10.1186/s12977-015-0193-1
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发表时间：
2015-08-08
期刊：
影响因子：
3.3
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Nitta T;Ha D;Galvez F;Miyazawa T;Fan H
考拉逆转录病毒是一种可引起淋巴瘤的考拉内源性和外源性逆转录病毒。对于许多其他伽玛逆转录病毒，KoRV基因组可能编码另一种形式的Gag蛋白，Glyco-Gag。在这项研究中，使用了一种简便的体外评估KoRV感染性的方法：使用Derse细胞(最初是为了寻找具有感染性的异嗜性小鼠白血病样病毒而开发的)。用DERSE和其他人类细胞株(HEK293T)感染，没有发现KoRV表达GAG的证据，无论是在GAG蛋白的表达上，还是在假定的GAG阅读框突变时感染性的变化上都没有发现证据。由于糖链GAG介导了Moloney鼠白血病病毒对限制因子APOBEC3的抗性，因此研究了KoRV(wt或假想的糖链突变体)对小鼠(MA3)或人APOBEC3限制性内切酶的敏感性。MA3和hA3G均能有效抑制KoRV的感染性。有趣的是，在反转录过程中，hA3G限制伴随着广泛的G-→-A超突变，而MA3限制则没有。Glyco-Gag状态不影响结果。这些结果表明，hA3G和MA3对KoRV的APOBEC3限制机制不同(脱氨基依赖和非依赖)，Glyco-Gag不起作用。本文的在线版本(doi：10.1186/s12977-015-0193-1)包含补充材料，授权用户可以使用。
Koala retrovirus (KoRV) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. As for many other gammaretroviruses, the KoRV genome can potentially encode an alternate form of Gag protein, glyco-gag. In this study, a convenient assay for assessing KoRV infectivity in vitro was employed: the use of DERSE cells (initially developed to search for infectious xenotropic murine leukemia-like viruses). Using infection of DERSE and other human cell lines (HEK293T), no evidence for expression of glyco-gag by KoRV was found, either in expression of glyco-gag protein or changes in infectivity when the putative glyco-gag reading frame was mutated. Since glyco-gag mediates resistance of Moloney murine leukemia virus to the restriction factor APOBEC3, the sensitivity of KoRV (wt or putatively mutant for glyco-gag) to restriction by murine (mA3) or human APOBEC3s was investigated. Both mA3 and hA3G potently inhibited KoRV infectivity. Interestingly, hA3G restriction was accompanied by extensive G → A hypermutation during reverse transcription while mA3 restriction was not. Glyco-gag status did not affect the results. These results indicate that the mechanisms of APOBEC3 restriction of KoRV by hA3G and mA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction. The online version of this article (doi:10.1186/s12977-015-0193-1) contains supplementary material, which is available to authorized users.
影响因子：
3.7
作者：
Stieler K;Fischer N
通讯作者：
Fischer N
影响因子：
3.3
作者：
Stoye JP;Silverman RH;Boucher CA;Le Grice SF
通讯作者：
Le Grice SF