Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Virology. 2011 Oct 10;419(1):24-42. doi: 10.1016/j.virol.2011.07.017. Epub 2011 Aug 25.
The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication.
人类载脂蛋白 B mRNA 编辑酶催化多肽样 3（APOBEC3；A3）家族蛋白（A3A-H）已知可限制各种逆转录病毒和逆转录元件，但恒河猴 A3 蛋白的完整组成仍不清楚。我们报告了从恒河猴（rhA3A）中分离和鉴定 hA3A 同源物，并表明恒河猴和人类 A3 基因是同源的。RhA3A 在激活的 CD4+T 细胞中高水平表达，在猴组织中广泛表达，并在存在人类免疫缺陷病毒（HIV-1）和猴免疫缺陷病毒（SHIV）基因组的情况下被降解。我们的结果表明，rhA3A 是 SHIVΔvif 的有效抑制剂，对 HIV-1Δvif 的抑制作用较小。与 hA3A 不同，rhA3A 不会抑制腺相关病毒 2（AAV-2）复制和 L1 逆转座。这些数据表明灵长类动物 A3A 的病毒特异性发生了进化转变，并首次提供了灵长类 A3A 可以抑制慢病毒复制的证据。
