Santiago Mario L, Montano Mauricio, Benitez Robert, Messer Ronald J, Yonemoto Wes, Chesebro Bruce, Hasenkrug Kim J, Greene Warner C
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
Science. 2008 Sep 5;321(5894):1343-6. doi: 10.1126/science.1161121.
Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.
Friend病毒3型抗性基因（Rfv3）是一个常染色体基因，编码一种抗性性状，该性状会影响逆转录病毒中和抗体反应及病毒血症。尽管经过30年的广泛研究，Rfv3的分子身份仍然难以确定。在此，我们证明Rfv3由载脂蛋白B mRNA编辑酶催化多肽样3（Apobec3）编码。Apobec3定位于与Rfv3相同的染色体区域，并且对包括HIV在内的逆转录病毒具有广泛的抑制活性。不仅Apobec3基因失活会使Rfv3抗性小鼠转变为易感表型，而且还发现Apobec3在Rfv3易感品系中因异常信使RNA剪接而天然失活。Apobec3与中和抗体反应之间的联系突显了一种可能延伸至HIV及其他人类逆转录病毒感染的宿主保护的Apobec3依赖性机制。
