Fig. 3

CST and the evolutionary arms race between viruses and hosts. a A3 as a barrier restricting CST. The lentivirus X infects the host A, and the Vif protein of virus X antagonizes the anti-viral A3 protein of host A. a Left When the Vif of virus X antagonizes not only anti-viral A3 of host A but also that of host B, a candidate for the new host, virus X can be successfully transferred from host A to host B without anti-viral restriction mediated by A3 of host B. a Right On the other hand, if the Vif protein of virus X is unable to antagonize anti-viral A3 of host C, another candidate for the new host, the anti-viral A3 of host C plays a role in restricting the CST of virus X from host A to host C. For a successful CST, the virus X evolves to adapt to host C and its Vif acquires the ability to antagonize host C’s anti-viral A3 (“Adaptive evolution” in this panel). As a result, a nascent species virus, the virus Y, has emerged and infects host C. b The concept of an evolutionary arms race between lentiviruses (Vif) and hosts (A3). In the past, an ancestral host (the host Y) was infected with an ancestral pathogenic virus (the virus X) and an anti-viral A3 protein of host Y was antagonized by the Vif protein of virus X (1). To escape from the pathogenic infection of virus X, the host A3 acquires certain mutations to be resistant to the degradation mediated by the virus X Vif, resulting in the emergence of a novel host, the host Y′ (2). Although the anti-viral A3 of the host Y′ is resistant to the virus X Vif (3), the virus X Vif acquires mutations to adapt to the host Y′ (4). Then, a novel virus, the virus X′, emerges and its Vif is able to antagonize an anti-viral A3 of the host Y′ (5). Subsequently, similar to the process of (1) to (5), the selective pressure by the virus X′ produces the host Y″ of which A3 is resistant to the virus X′ Vif (6 and 7), while the virus X′ evolves to antagonize the host Y″ A3 and becomes the virus X″ (8 and 9). Such an “arms race” between lentiviruses and hosts has evolutionarily occurred over a long period of time (10). It is speculated that this process might trigger the duplication of A3 genes in mammals. After n-times arms races, in the present, the host Yⁿ encodes multiple anti-viral A3 proteins, while the Vif of the virus Xⁿ antagonizes them (11)