A naturally occurring feline APOBEC3 variant that loses anti-lentiviral activity by lacking two amino acid residues
A naturally occurring feline APOBEC3 variant that loses anti-lentiviral activity by lacking two amino acid residues
复制标题
DOI：
10.1099/jgv.0.001046
复制
发表时间：
2018-05-01
影响因子：
3.8
通讯作者：
Sato, Kei
中科院分区：
文献类型：
--
作者：
Konno, Yoriyuki;Nagaoka, Shumpei;Sato, Kei
载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC3）是一种限制慢病毒复制的哺乳动物蛋白质。在人类、旧大陆猴和家猫中已观察到哺乳动物APOBEC3基因的多种多态性；然而，其他哺乳动物中APOBEC3基因的遗传多样性仍未被研究。在此，我们在一只欧亚猞猁（Lynx lynx）中鉴定出猫APOBEC3Z3基因的一种新型单倍型，APOBEC3Z3基因是一种限制猫免疫缺陷病毒（FIV）复制的基因。与先前鉴定的猞猁APOBEC3Z3（单倍型I）相比，新序列（单倍型II）有两个氨基酸缺失（016和H17）以及一个非同义替换（R68Q）。有趣的是，猞猁APOBEC3Z3单倍型II不抑制FIV感染性，而单倍型I则可以。诱变实验进一步表明，缺失两个氨基酸（016和H17）会导致抗FIV活性丧失。本报告证明，一种自然发生的APOBEC3变体通过缺失两个氨基酸残基而失去抗慢病毒活性。
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) is a mammalian protein that restricts lentiviral replication. Various polymorphisms of mammalian APOBEC3 genes have been observed in humans, Old World monkeys and domestic cats; however, the genetic diversity of APOBEC3 genes in other mammals remains unaddressed. Here we identify a novel haplotype of the feline APOBEC3Z3 gene, an APOBEC3 gene that restricts feline immunodeficiency virus (FIV) replication, in a Eurasian lynx (Lynx lynx). Compared to the previously identified lynx APOBEC3Z3 (haplotype I), the new sequence (haplotype II) harbours two amino acid deletions (016 and H17) and a nonsynonymous substitution (R68Q). Interestingly, lynx APOBEC3Z3 haplotype II does not suppress FIV infectivity, whereas haplotype I does. Mutagenesis experiments further revealed that deleting two amino acids (016 and H17) causes anti-FIV activity loss. This report demonstrates that a naturally occurring APOBEC3 variant loses anti-lentiviral activity through the deletion of two amino acid residues.