Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Retrovirology. 2018 Apr 10;15(1):31. doi: 10.1186/s12977-018-0414-5.
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals.
Here we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved.
To the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.
载脂蛋白 B mRNA 编辑酶催化多肽样 3（APOBEC3；A3）基因家族仅出现在哺乳动物基因组中。一些 A3 蛋白可以整合到后代病毒粒子中，并抑制慢病毒复制。反过来，慢病毒病毒感染性因子（Vif）通过降解 A3 蛋白来抵消 A3 介导的抗病毒作用。最近的研究表明，慢病毒 vif 基因进化是为了对抗哺乳动物 APOBEC3 蛋白，并进一步提出 Vif-A3 相互作用可能有助于确定哺乳动物中跨种慢病毒传播的共同进化史。
在这里，我们研究了两种新世界猫科动物，美洲狮（Puma concolor）和山猫（Lynx rufus）及其慢病毒之间的共同进化关系，这些慢病毒被指定为美洲狮慢病毒（PLV）。我们证明，PLV-A Vif 抵消了美洲狮和山猫 APOBEC3Z3（A3Z3）的抗病毒作用，而 PLV-B Vif 仅抵消了美洲狮 A3Z3。PLV-B Vif 的种特异性与猫科动物属中的美洲狮、山猫和猎豹的系统发育关系无关。我们揭示了美洲狮和山猫 A3Z3 中第 178 位氨基酸在蛋白质表面暴露，并决定了对 PLV-B Vif 介导的降解的敏感性。此外，尽管美洲狮和山猫 A3Z3 基因都是多态的，但它们对 PLV Vif 介导的降解的敏感性/抗性是保守的。
据我们所知，这是第一项表明宿主 A3 蛋白强烈控制跨属慢病毒传播的研究。我们的研究结果首次提供了证据，表明慢病毒和哺乳动物之间的共同进化军备竞赛发生在新世界。
