A conflict of interest: the evolutionary arms race between mammalian APOBEC3 and lentiviral Vif

Abstract

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins are mammalian-specific cellular deaminases and have a robust ability to restrain lentivirus replication. To antagonize APOBEC3-mediated antiviral action, lentiviruses have acquired viral infectivity factor (Vif) as an accessory gene. Mammalian APOBEC3 proteins inhibit lentiviral replication by enzymatically inserting G-to-A hypermutations in the viral genome, whereas lentiviral Vif proteins degrade host APOBEC3 via the ubiquitin/proteasome-dependent pathway. Recent investigations provide evidence that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins. In corollary, mammalian APOBEC3 genes are under Darwinian selective pressure to escape from antagonism by Vif. Based on these observations, it is widely accepted that lentiviral Vif and mammalian APOBEC3 have co-evolved and this concept is called an “evolutionary arms race.” This review provides a comprehensive summary of current knowledge with respect to the evolutionary dynamics occurring at this pivotal host-virus interface.

DGINN, an automated and highly-flexible pipeline for the Detection of Genetic INNovations on protein-coding genes

“…A gene was considered as part of a multigene family if it had at least one paralogue with over 50% reciprocal identity amongst primates (according to Ensembl). A member of the APOBEC3 gene family was also included as an extreme example of genes involved in virus-host evolutionary arms-races and that have undergone numerous genetic innovations (Nakano et al 2017, Etienne et al, 2015, Desimmie et al, 2014; Sawyer et al, 2004). Another example of multigene family member included is HERC5, which exhibits antiviral activity (reviewed in Kluge et al 2005) and described in the literature as evolving under positive selection (Woods et al, 2014).…”

“…By further analyzing all the retrieved paralogues, we observed two mixes: in the APOBEC3F query, group 2 contained APOBEC3D and APOBEC3B sequences and APOBEC3B was split in two groups, and a similar pattern occurred in the GBP5 query, with GBP1 in groups 2 and 3 (Table 4). These errors could be explained by the particularly complicated evolutionary histories of those two expanded gene families during primate evolution (Münk et al, 2012, Desimmie et al, 2014, Nakano et al, 2017. This highlights a need to improve the management of the detection of duplication events in further versions of DGINN.…”

“…duplications and subsequent diversification(Daugherty and Zanders 2019). For example, many antiviral effectors, also called restriction factors, belong to multigene families, where duplicated copies have evolved varied antiviral functions and/or virus-host interfaces/determinants, such as the Mx (Myxovirus resistance) Dynamin Like GTPases Mx1 and Mx2(Haller et al, 2015), the guanylate-binding proteins GBPs(Tretina et al, 2019, Huang et al, 2019, the primate APOBEC3 gene family(Munk et al., 2012, Desimmie et al, 2014, Etienne et al, 2015, Nakano et al 2017 or the genes from the TRIM family.…”

Rapid evolution of antiviral APOBEC3 genes driven by the conflicts with ancient retroviruses

“…Such conflicts between A3 proteins and modern viruses (particularly retroviruses) have been reported in a broad range of mammalian species and viruses infecting with them (reviewed in ref. 13 ).…”

“…Based on the sequences of their Z domains, A3 genes are classified into three classes, A3Z1, A3Z2 and, A3Z3 (reviewed in refs. 7,13,24 ). For example, human A3 genes are composed of 7 paralogs (A3A, A3B, A3C, A3D, A3F, A3G , and A3H ).…”