Feline Tetherin Efficiently Restricts Release of Feline Immunodeficiency Virus but Not Spreading of Infection
Feline Tetherin Efficiently Restricts Release of Feline Immunodeficiency Virus but Not Spreading of Infection
复制标题
DOI：
10.1128/jvi.00071-11
复制
发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Willett, Brian J.
中科院分区：
文献类型：
--
作者：
Dietrich, Isabelle;McMonagle, Elizabeth L.;Willett, Brian J.
家猫遭受逆转录病毒科所有三个亚科的感染：慢病毒(猫免疫缺陷病毒[FIV])、伽马逆转录病毒(猫白血病病毒[FeLV])和SpumaretroVirus(猫泡沫病毒[FFV])。因此，猫提供了一个关于宿主-逆转录病毒关系的进化和内在/先天免疫机制发展的洞察力。Tetherin(BST-2)是一种干扰素诱导的跨膜蛋白，可抑制被包裹的病毒从感染细胞中释放。在这里，我们表征了猫科动物的Tetherin同源物，并评估了它对FIV复制的影响。Tetherin在许多猫细胞系中都有表达，并在干扰素诱导下表达，干扰素包括α-干扰素、干扰素-omega和干扰素-γ。与人类Tetherin一样，猫Tetherin显示出对FIV和HIV-1颗粒释放的有效抑制；然而，这种活性抵抗了HIV-1 VPU或FIV Env和“Orfa”蛋白的拮抗作用。此外，由于FIV全基因组在TRAN中的过度表达不能克服猫科动物的Tetherin，这些数据表明FIV缺乏功能Tetherin拮抗剂。然而，当在猫细胞系中稳定表达时，Tetherin并不能消除FIV的复制；事实上，在感染FIV细胞培养适应(CD134非依赖)FIV(FIV FCA-F14和FIV PCO-COLV)株的Tetherin表达细胞中，合胞体的形成显著增强。因此，虽然Tetherin可以阻止新生病毒颗粒的释放，但在存在丰富的病毒受体的情况下，细胞间的传播仍然有效，并且Tetherin上调可能会促进合胞体的形成。因此，Tetherin在体内的表达可能会促进病毒变体的选择性扩张，从而能够更有效地在细胞之间传播。
Domestic cats endure infections by all three subfamilies of the retroviridae: lentiviruses (feline immunodeficiency virus [FIV]), gammaretroviruses (feline leukemia virus [FeLV]), and spumaretroviruses (feline foamy virus [FFV]). Thus, cats present an insight into the evolution of the host-retrovirus relationship and the development of intrinsic/innate immune mechanisms. Tetherin (BST-2) is an interferon-inducible transmembrane protein that inhibits the release of enveloped viruses from infected cells. Here, we characterize the feline homologue of tetherin and assess its effects on the replication of FIV. Tetherin was expressed in many feline cell lines, and expression was induced by interferons, including alpha interferon (IFN-alpha), IFN-omega, and IFN-gamma. Like human tetherin, feline tetherin displayed potent inhibition of FIV and HIV-1 particle release; however, this activity resisted antagonism by either HIV-1 Vpu or the FIV Env and "OrfA" proteins. Further, as overexpression of complete FIV genomes in trans could not overcome feline tetherin, these data suggest that FIV lacks a functional tetherin antagonist. However, when expressed stably in feline cell lines, tetherin did not abrogate the replication of FIV; indeed, syncytium formation was significantly enhanced in tetherin-expressing cells infected with cell culture-adapted (CD134-independent) strains of FIV (FIV Fca-F14 and FIV Pco-CoLV). Thus, while tetherin may prevent the release of nascent viral particles, cell-to-cell spread remains efficient in the presence of abundant viral receptors and tetherin upregulation may enhance syncytium formation. Accordingly, tetherin expression in vivo may promote the selective expansion of viral variants capable of more efficient cell-to-cell spread.