A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of domestic cats mediates infection of a pathogenic variant of feline leukemia virus.
A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of domestic cats mediates infection of a pathogenic variant of feline leukemia virus.
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家猫血清中存在的内源性逆转录病毒（FeLIX）的可溶性包膜蛋白介导猫白血病病毒致病性变体的感染。
DOI：
10.1099/vir.0.071688-0
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发表时间：
2015
影响因子：
3.8
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Sakaguchi;S.;Shojima;T.;Fukui;D. and Miyazawa;T.
T淋巴细胞猫白血病病毒(FeLV-T)是猫T淋巴细胞白血病病毒的高致病性变异株，可引起猫严重的免疫抑制。FeLV-T是融合缺陷的，因为在它的PHQ基序中，在包膜蛋白N端的一个伽马逆转录病毒共识基序中，组氨酸被天冬氨酸取代。FeLV-T感染需要由内源性FeLV编码的截短包膜蛋白Felix反式激活感染性，需要Pit1结合Felix。虽然Pit1存在于猫的大多数组织中，但Felix的表达仅限于淋巴器官中的某些细胞。因此，FeLV-T的宿主细胞范围被认为仅限于表达Felix的细胞。然而，由于Felix是一种可溶性因子，并且在淋巴器官中有结构性表达，我们推测它存在于血液中，并使用伪型分析方法评估了它在各种哺乳动物血清中的活性。我们证明了猫血清在功能水平上具有Felix活性，这表明Felix存在于血液中，FeLV-T可能能够感染表达Pit1的细胞，而不管FeLIX在体内的表达情况。此外，血清中的Felix活性只在家猫身上检测到，而在其他被测试的猫科动物中没有检测到。据我们所知，这是首次证明内源性逆转录病毒的大量截短包膜蛋白在血液中循环，以促进致病性外源性逆转录病毒的感染。
T-lymphotropic feline leukemia virus (FeLV-T), a highly pathogenic variant of FeLV, induces severe immunosuppression in cats. FeLV-T is fusion defective because in its PHQ motif, a gammaretroviral consensus motif in the N terminus of an envelope protein, histidine is replaced with aspartate. Infection by FeLV-T requires FeLIX, a truncated envelope protein encoded by an endogenous FeLV, for transactivation of infectivity and Pit1 for binding FeLIX. Although Pit1 is present in most tissues in cats, the expression of FeLIX is limited to certain cells in lymphoid organs. Therefore, the host cell range of FeLV-T was thought to be restricted to cells expressing FeLIX. However, because FeLIX is a soluble factor and is expressed constitutively in lymphoid organs, we presumed it to be present in blood and evaluated its activities in sera of various mammalian species using a pseudotype assay. We demonstrated that cat serum has FeLIX activity at a functional level, suggesting that FeLIX is present in the blood and that FeLV-T may be able to infect cells expressing Pit1 regardless of the expression of FeLIXin vivo. In addition, FeLIX activities in sera were detected only in domestic cats and not in other feline species tested. To our knowledge, this is the first report to prove that a large amount of truncated envelope protein of endogenous retrovirus is circulating in the blood to facilitate the infection of a pathogenic exogenous retrovirus.