Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Virology. 2014 Apr;454-455:215-26. doi: 10.1016/j.virol.2014.02.022. Epub 2014 Mar 13.
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.
人类编码七种 APOBEC3（A3A-A3H）胞嘧啶脱氨酶蛋白，它们在表达谱、偏好的核苷酸识别序列和限制 RNA 和 DNA 病毒的能力上有所不同。我们在多种疱疹病毒基因组中鉴定出了 APOBEC3 热点。为了确定宿主 APOBEC3 对疱疹病毒生物学的影响，我们研究了鼠 APOBEC3（mA3）是否限制鼠γ疱疹病毒 68（MHV68）。当转染病毒基因组时，几种人 APOBEC3 蛋白（而非 mA3）会损害病毒复制。当 A3A 和 A3B 活性位点发生突变时，这种限制就会被消除。有趣的是，如果传染性 DNA 是由病毒粒子提供的，则 A3A、A3B、A3C 和 A3DE 的病毒限制作用就会丧失。在缺乏 mA3 的小鼠中，MHV68 的发病机制，包括肺部复制和脾脏潜伏，并未改变。我们推断 mA3 不会限制野生型 MHV68，而人类 A3s 的限制作用可能在疱疹病毒复制过程中受到限制。
