Division of Virology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom.
Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5166-71. doi: 10.1073/pnas.0913650107. Epub 2010 Mar 1.
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 TRIM5alpha, 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.
异嗜性鼠白血病病毒相关病毒 (XMRV) 是一种新发现的γ逆转录病毒，与前列腺癌和慢性疲劳综合征有关。因此，这种病毒是一种重要的潜在人类病原体，因此，了解其宿主细胞嗜性至关重要。有趣的是，已从患者来源的外周血单核细胞中回收了传染性病毒。这些细胞表达几种抗病毒限制因子，能够抑制广泛的逆转录病毒，包括其他γ逆转录病毒的复制。这就提出了这样一种可能性，即类似于 HIV，XMRV 可能已经获得了对限制的抗性。因此，我们研究了 XMRV 对一系列不同限制因子的敏感性。我们发现，人 APOBEC3 和 tetherin 蛋白都能够阻止 XMRV 的复制。然而，人 TRIM5alpha 的表达对病毒感染性没有影响。没有证据表明 XMRV 表达了克服限制的对策。此外，非人类物种的因子，包括鼠 APOBEC3、tetherin 和 Fv1 蛋白，也抑制了病毒。这些结果对预测 XMRV 复制的自然靶细胞、将感染与病毒的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。
