Retroviruses and Cancer: Coevolution and Genetic Exchanges Between the Viral and the Host Genomes

Retroviruses, after their genomes are integrated into the host genome, replicate through host cell replication. In this hitchhiking phase, their only way of increasing their fitness is to encourage the host cell to have unregulated, rapid cell replication. The v-Src gene in avian sarcoma virus and the v-sis gene in the simian sarcoma virus were originally mined from the host genome by the virus to increase host cell replication rate, with the corresponding host cellular counterparts c-Src (non-receptor tyrosine kinase) and c-sis (platelet-derived growth factor). The resulting out-of-control replication ultimately would lead to cancer. The battle between the host and the retroviruses left many retroviral corpses known as endogenous retroviruses, and the host occasionally domesticates retroviral genes. The syncytins (whose fusogenic function is crucial for the trophoblast fusion and the formation of a syncytium during placenta morphogenesis) and suppressyn (which serves the dual function of regulating syncytialization and host resistance against retroviruses) are examples of successful domestication. Syncytin-1 and suppressyn have each been “domesticated” independently multiple times by different mammalian lineages. Molecular phylogenetics is an essential tool for tracing the evolutionary trajectories of such genetic exchanges between retroviruses and their hosts and for determining the direction of the genetic exchange.