Humans encode seven APOBEC3 (A3A-A3H) cytidine deaminase proteins that differ in their expression profiles, preferred nucleotide recognition sequence and capacity for restriction of RNA and DNA viruses. We identified APOBEC3 hotspots in numerous herpesvirus genomes. To determine the impact of host APOBEC3 on herpesvirus biology in vivo, we examined whether murine APOBEC3 (mA3) restricts murine gammaherpesvirus 68 (MHV68). Viral replication was impaired by several human APOBEC3 proteins, but not mA3, upon transfection of the viral genome. The restriction was abrogated upon mutation of the A3A and A3B active sites. Interestingly, virus restriction by A3A, A3B, A3C, and A3DE was lost if the infectious DNA was delivered by the virion. MHV68 pathogenesis, including lung replication and splenic latency, was not altered in mice lacking mA3. We infer that mA3 does not restrict wild type MHV68 and restriction by human A3s may be limited in the herpesvirus replication process.

中文翻译：

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人类 APOBEC3 胞苷脱氨酶但不是鼠 APOBEC3 对鼠 gammaherpesvirus 68 复制的宿主限制。

人类编码七种 APOBEC3 (A3A-A3H) 胞苷脱氨酶蛋白，它们的表达谱、首选核苷酸识别序列以及限制 RNA 和 DNA 病毒的能力不同。我们在众多疱疹病毒基因组中确定了 APOBEC3 热点。为了确定宿主 APOBEC3 对体内疱疹病毒生物学的影响，我们检查了鼠 APOBEC3 (mA3) 是否限制鼠 gammaherpesvirus 68 (MHV68)。病毒基因组转染后，病毒复制会受到几种人类 APOBEC3 蛋白的影响，但 mA3 不会。该限制在 A3A 和 A3B 活性位点发生突变后被取消。有趣的是，如果感染性 DNA 是由病毒体传递的，则 A3A、A3B、A3C 和 A3DE 的病毒限制就会丢失。MHV68 发病机制，包括肺复制和脾潜伏期，在缺乏 mA3 的小鼠中没有改变。