Department of Chemistry, Wayne State University, Detroit, MI, 48202, USA.
Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Virology. 2019 Nov;537:104-109. doi: 10.1016/j.virol.2019.08.012. Epub 2019 Aug 13.
APOBEC3 family of DNA-cytosine deaminases inactivate and mutate several human viruses. We constructed a human cell line that is inducible for EGFP-tagged APOBEC3A and found A3A predominantly in the nuclei. When these cells were infected with Herpes Simplex Virus-1, virus titer was unaffected by A3A expression despite nuclear virus replication. When A3A expression and virus infection were monitored, A3A was found predominantly to be nuclear in infected cells up to 3 h post-infection, but was predominantly cytoplasmic by 12 h. This effect did not require the whole virus, and could be reproduced using the UL39 gene of the virus which codes for a subunit of the viral ribonucleotide reductase. These results are similar to the reported exclusion of APOBEC3B by Epstein Barr virus ortholog of UL39, BORF2, but HSV1 UL39 gene product appears better at excluding A3A than A3B from nuclei.
APOBEC3 家族的 DNA-胞嘧啶脱氨酶使多种人类病毒失活和突变。我们构建了一种可诱导表达 EGFP 标记的 APOBEC3A 的人细胞系,发现 A3A 主要存在于细胞核中。当这些细胞感染单纯疱疹病毒-1 时,尽管存在核内病毒复制,但 A3A 的表达并不影响病毒滴度。当监测 A3A 的表达和病毒感染时,发现 A3A 在感染细胞中至感染后 3 小时主要存在于核内,但在 12 小时后主要存在于细胞质中。这种效应不需要整个病毒,并且可以使用病毒的 UL39 基因来重现,该基因编码病毒核糖核苷酸还原酶的一个亚基。这些结果与报道的 EBV 同源物 UL39 的 BORF2 排除 APOBEC3B 相似,但 HSV1 UL39 基因产物似乎比 A3B 更能将 A3A 从核内排除。