The DNA Cytosine Deaminase APOBEC3G is upregulated during Human Cytomegalovirus infection

The Apolipoprotein B Editing Enzyme Catalytic subunit 3 (APOBEC3) is a family of DNA cytosine deaminases that mutate and inactivate viral genomes by single-strand DNA editing, with important roles in innate immunity and cancer. It has been demonstrated that APOBEC3 interfere with viral replication of RNA and DNA viruses, but its role during Human Cytomegalovirus (HCMV) replication has never been investigated. APOBEC3 is able to counteract viral replication increasing mutation rates in viral genome. On the other hand, HCMV displays high variability limited to distinct parts of the genome. In this study we analysed the impact of HCMV infection on APOBEC3 expression and activity. We observed that APOBEC3G is upregulated by HCMV infection in primary Foreskin Human Fibroblast (HFF) at both mRNA and at protein level. However, although strongly induced, the speciﬕc knockdown of APOBEC3G does not negatively affect HCMV virus propagation. It has been previously reported that Interferon type I (IFN-I) is able to induce APOBEC3 expression. In agreement with these results, we demonstrated that the induction of APOBEC3G expression upon HCMV infection is IFN-I mediated, produced early during HCMV infection. Therefore, understanding the role of this deaminase on the immune response against HCMV has become pivotal.