Bogerd Hal P, Wiegand Heather L, Doehle Brian P, Lueders Kira K, Cullen Bryan R
Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Nucleic Acids Res. 2006 Jan 10;34(1):89-95. doi: 10.1093/nar/gkj416. Print 2006.
While the ability of APOBEC3G to reduce the replication of a range of exogenous retroviruses is now well established, recent evidence has suggested that APOBEC3G can also inhibit the replication of endogenous retrotransposons that bear long terminal repeats. Here, we extend this earlier work by showing that two other members of the human APOBEC3 protein family, APOBEC3B and APOBEC3A, can reduce retrotransposition by the intracisternal A-particle (IAP) retrotransposon in human cells by 20-fold to up to 100-fold, respectively. This compares to an approximately 4-fold inhibition in IAP retrotransposition induced by APOBEC3G. While both APOBEC3G and APOBEC3B specifically interact with the IAP Gag protein in co-expressing cells, and induce extensive editing of IAP reverse transcripts, APOBEC3A fails to package detectably into IAP virus-like particles and does not edit IAP reverse transcripts. These data, which identify human APOBEC3A as a highly potent inhibitor of LTR-retrotransposon function, are the first to ascribe a biological activity to APOBEC3A. Moreover, these results argue that APOBEC3A inhibits IAP retrotransposition via a novel mechanism that is distinct from, and in this case more effective than, the DNA editing mechanism characteristic of APOBEC3G and APOBEC3B.
虽然载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G）降低一系列外源性逆转录病毒复制的能力现已得到充分证实，但最近有证据表明，APOBEC3G还能抑制带有长末端重复序列的内源性逆转座子的复制。在此，我们扩展了这项早期研究，表明人类APOBEC3蛋白家族的另外两个成员，即载脂蛋白B mRNA编辑酶催化多肽样蛋白3B（APOBEC3B）和载脂蛋白B mRNA编辑酶催化多肽样蛋白3A（APOBEC3A），可分别将人类细胞中脑内A颗粒（IAP）逆转座子的逆转座作用降低20倍至100倍。相比之下，APOBEC3G对IAP逆转座作用的抑制约为4倍。虽然APOBEC3G和APOBEC3B在共表达细胞中均与IAP Gag蛋白特异性相互作用，并诱导IAP逆转录产物的广泛编辑，但APOBEC3A无法被检测到包装进IAP病毒样颗粒中，也不编辑IAP逆转录产物。这些数据将人类APOBEC3A鉴定为LTR逆转座子功能的高效抑制剂，首次赋予了APOBEC3A一种生物学活性。此外，这些结果表明，APOBEC3A通过一种不同于APOBEC3G和APOBEC3B的DNA编辑机制的新机制抑制IAP逆转座作用，在这种情况下更有效。
