Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors
Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors
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DOI：
10.1073/pnas.0913650107
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发表时间：
2010-03-16
影响因子：
11.1
通讯作者：
Bishop, Kate N.
中科院分区：
文献类型：
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作者：
Groom, Harriet C. T.;Yap, Melvyn W.;Bishop, Kate N.
异嗜性小鼠白血病病毒相关病毒（XMRV）是最近发现的一种与前列腺癌和慢性疲劳综合征有关的γ -逆转录病毒。因此，这种病毒是一种重要的潜在人类病原体，因此，了解其宿主细胞趋向性至关重要。有趣的是，传染性病毒已从患者外周血单个核细胞中恢复。这些细胞表达多种抗病毒限制因子，能够抑制多种逆转录病毒的复制，包括其他γ逆转录病毒。这就提出了一种可能性，与HIV类似，XMRV可能已经获得了对限制的抵抗力。因此，我们研究了XMRV对一系列不同限制因素的易感性。我们发现人类APOBEC3和tetherin蛋白都能够阻断XMRV的复制。然而，人TRIM5 α的表达对病毒的感染性没有影响。没有证据表明XMRV表达了克服限制的对策。此外，病毒被来自非人类物种的因子抑制，包括小鼠Apobec3、tetherin和Fv1蛋白。这些结果对于预测XMRV复制的自然靶细胞，将感染与病毒致病性和病理学联系起来，以及设计用于研究XMRV相关疾病的模型系统具有重要意义。
Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. Intriguingly, infectious virus has been recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors that are capable of inhibiting the replication of a wide range of retroviruses, including other gamma retroviruses. This raises the possibility that, similar to HIV, XMRV may have acquired resistance to restriction. We therefore investigated the susceptibility of XMRV to a panel of different restriction factors. We found that both human APOBEC3 and tetherin proteins are able to block XMRV replication. Expression of human TRIM5 alpha, however, had no effect on viral infectivity. There was no evidence that XMRV expressed countermeasures to overcome restriction. In addition, the virus was inhibited by factors from nonhuman species, including mouse Apobec3, tetherin, and Fv1 proteins. These results have important implications for predicting the natural target cells for XMRV replication, for relating infection to viral pathogenicity and pathology, and for the design of model systems with which to study XMRV-related diseases.