Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection.

Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection.
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DOI:
10.1126/science.1161121
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发表时间:
2008-09-05
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Greene WC
Greene WC
中科院分区:
其他
文献类型:
--
作者:
Santiago ML;Montano M;Benitez R;Messer RJ;Yonemoto W;Chesebro B;Hasenkrug KJ;Greene WC

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从朋友病毒3(Rfv3)恢复是编码影响逆转录病毒中和抗体应答和病毒血症的抗性性状的单个常染色体基因。尽管进行了30年的广泛研究,但Rfv3的分子身份仍然难以捉摸。在这里,我们证明Rfv3是由Apobec3编码的。Apobec3定位于与Rfv3相同的染色体区域,并对包括HIV在内的逆转录病毒具有广泛的抑制活性。不仅Apobec3的遗传失活将Rfv3抗性小鼠转化为易感表型,而且发现Apobec3在Rfv3易感品系中通过异常mRNA剪接而自然失活。Apobec3和中和抗体反应之间的联系突出了Apobec3依赖的宿主保护机制,可能扩展到HIV和其他人类逆转录病毒感染。
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 found to be naturally disabled by aberrant mRNA 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.
DOI: 10.1016/s1097-2765(03)00353-8
发表时间: 2003-09-01
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影响因子: 16
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