Persistent Friend virus replication and disease in Apobec3-deficient mice expressing functional B-cell-activating factor receptor.
Persistent Friend virus replication and disease in Apobec3-deficient mice expressing functional B-cell-activating factor receptor.
复制标题
表达功能性 B 细胞激活因子受体的 Apobec3 缺陷小鼠中的持久性朋友病毒复制和疾病。
DOI：
10.1128/jvi.01838-10
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发表时间：
2011
影响因子：
5.4
通讯作者：
Greene,WarnerC
中科院分区：
文献类型：
--
作者：
Santiago,MarioL;Smith,DianaS;Barrett,BradleyS;Montano,Mauricio;Benitez,RobertL;Pelanda,Roberta;Hasenkrug,KimJ;Greene,WarnerC
Rfv 3是一种常染色体显性基因，通过限制病毒血症和促进更有效的中和抗体应答来影响Friend逆转录病毒（FV）感染抗性小鼠的恢复。我们以前报道Rfv 3是由Apobec 3编码的，Apobec 3是一种先天性逆转录病毒限制因子。然而，最近的研究表明，在感染后28天（dpi）的高病毒血症的Rfv 3易感表型更主要地由B细胞活化因子受体（BAFF-R）控制，BAFF-R是一种与Rfv 3基因连锁但位于Rfv 3基因定位区域之外的基因。虽然一个原型Rfv 3易感小鼠品系A/WySn确实含有功能障碍的BAFF-R，但根据基因分型和B细胞免疫表型确定，另外两个Rfv 3易感品系BALB/c和A.BY表达功能性BAFF-R基因。此外，在（C57 BL/6 [B6] × BALB/c）F1和（B6 × A.BY）F1小鼠中的反式互补研究表明，B6 Apobec 3基因显著影响28 dpi时FV病毒血症、细胞感染和疾病的恢复。最后，原型B6、A.BY、A/WySn和BALB/c小鼠品系的Rfv 3表型与Apobec 3 mRNA表达水平相关。总的来说，这些发现反对BAFF-R多态性作为解释Rfv 3恢复表型的主导机制的普遍性，并进一步加强了Apobec 3编码Rfv 3的证据。
Rfv3is an autosomal dominant gene that influences the recovery of resistant mice from Friend retrovirus (FV) infection by limiting viremia and promoting a more potent neutralizing antibody response. We previously reported thatRfv3is encoded byApobec3, an innate retrovirus restriction factor. However, it was recently suggested that theRfv3 susceptible phenotype of high viremia at 28 days postinfection (dpi) was more dominantly controlled by the B-cell-activating factor receptor (BAFF-R), a gene that is linked to but located outside the genetically mapped region containingRfv3. Although one prototypicalRfv3susceptible mouse strain, A/WySn, indeed contains a dysfunctional BAFF-R, two otherRfv3susceptible strains, BALB/c and A.BY, express functional BAFF-R genes, determined on the basis of genotyping and B-cell immunophenotyping. Furthermore, transcomplementation studies in (C57BL/6 [B6] × BALB/c)F1and (B6 × A.BY)F1mice revealed that the B6Apobec3gene significantly influences recovery from FV viremia, cellular infection, and disease at 28 dpi. Finally, theRfv3phenotypes of prototypic B6, A.BY, A/WySn, and BALB/c mouse strains correlate with reportedApobec3mRNA expression levels. Overall, these findings argue against the generality ofBAFF-Rpolymorphisms as a dominant mechanism to explain theRfv3recovery phenotype and further strengthen the evidence thatApobec3encodesRfv3.