内源性逆转录病毒(ERV)是祖先病毒感染的残余物。猫白血病病毒(FeLV)是家猫的外源性和内源性逆转录病毒。它分为几个子组(A,B,C,D,E,和T)基于病毒受体干扰特性或受体使用。ERV衍生的分子有益于动物,赋予对传染病的抵抗力。然而,内源性FeLV(enFeLV)的包膜缺陷(env)基因编码的可溶性蛋白在FeLV亚群T感染中起辅助因子的作用。因此,该基因是否有助于病毒感染尚不清楚.基于ERV衍生分子的性质,我们假设有缺陷的env基因具有对宿主有利的抗病毒活性,因为FeLV亚群B(FeLV-B),来自enFeLVenv的重组病毒,仅限于家猫之间的病毒传播。当测试来自enFeLV的可溶性截短Env蛋白对enFeLV和FeLV-B的抑制作用时,他们抑制病毒感染。值得注意的是,这种抗病毒机制被扩展到长臂猿白血病病毒感染,考拉逆转录病毒A,和赫维翼龙γ病毒。尽管这些病毒使用猫磷酸盐转运蛋白1(fePit1)和磷酸盐转运蛋白2作为受体,抑制机制涉及fepit1依赖性方式的竞争性受体结合。受体使用的转变可能是为了避免抑制作用而发生的。总的来说,这些发现强调了来自enFeLV的可溶性截短Env蛋白作为抗逆转录病毒感染的限制因子的可能出现,并将有助于通过控制逆转录病毒传播来发展宿主免疫和抗病毒防御.IMPORTANCERAQ病毒在使用逆转录酶将RNA基因组转化为DNA方面是独特的,感染生殖细胞,并传给后代。许多古老的逆转录病毒序列被称为内源性逆转录病毒(ERV)。来源于ERV的可溶性Env蛋白作为辅助FeLV-T感染的辅因子发挥作用。然而,在这里,我们表明,可溶性Env蛋白表现出抗病毒活性,并通过竞争性受体结合提供对哺乳动物逆转录病毒感染的抗性。特别是,这一发现可以解释为什么在家猫中没有观察到FeLV-B传播。ERV衍生的分子可以在进化军备竞赛中有益于动物,强调ERV的双刃剑性质。
Endogenous retroviruses (ERVs) are remnants of ancestral viral infections. Feline leukemia virus (FeLV) is an exogenous and endogenous retrovirus in domestic cats. It is classified into several subgroups (A, B, C, D, E, and T) based on viral receptor interference properties or receptor usage. ERV-derived molecules benefit animals, conferring resistance to infectious diseases. However, the soluble protein encoded by the defective envelope (env) gene of endogenous FeLV (enFeLV) functions as a co-factor in FeLV subgroup T infections. Therefore, whether the gene emerged to facilitate viral infection is unclear. Based on the properties of ERV-derived molecules, we hypothesized that the defective env genes possess antiviral activity that would be advantageous to the host because FeLV subgroup B (FeLV-B), a recombinant virus derived from enFeLV env, is restricted to viral transmission among domestic cats. When soluble truncated Env proteins from enFeLV were tested for their inhibitory effects against enFeLV and FeLV-B, they inhibited viral infection. Notably, this antiviral machinery was extended to infection with the Gibbon ape leukemia virus, Koala retrovirus A, and Hervey pteropid gammaretrovirus. Although these viruses used feline phosphate transporter 1 (fePit1) and phosphate transporter 2 as receptors, the inhibitory mechanism involved competitive receptor binding in a fePit1-dependent manner. The shift in receptor usage might have occurred to avoid the inhibitory effect. Overall, these findings highlight the possible emergence of soluble truncated Env proteins from enFeLV as a restriction factor against retroviral infection and will help in developing host immunity and antiviral defense by controlling retroviral spread.IMPORTANCERetroviruses are unique in using reverse transcriptase to convert RNA genomes into DNA, infecting germ cells, and transmitting to offspring. Numerous ancient retroviral sequences are known as endogenous retroviruses (ERVs). The soluble Env protein derived from ERVs functions as a co-factor that assists in FeLV-T infection. However, herein, we show that the soluble Env protein exhibits antiviral activity and provides resistance to mammalian retrovirus infection through competitive receptor binding. In particular, this finding may explain why FeLV-B transmission is not observed among domestic cats. ERV-derived molecules can benefit animals in an evolutionary arms race, highlighting the double-edged-sword nature of ERVs.