Mechanisms of viral emergence

Domingo, Esteban

A biological feature relevant to emergence is the overlap that has been identified in several viruses between receptor-recognition sites and antigenic sites. The fact that some exposed amino acid residues are part of one or several epitopes for antibody binding, as well as part of the receptor-recognition domain, may favor the coevolution of host cell tropism and antigenicity [2, 3, 36, 58, 83] . Such overlap is, however, double-edged. It opens the possibility of pleiotropic effects of single mutations (that may affect positively or negatively more than one viral function), and of coevolution of phenotypic traits. However, it may also introduce additional evolutionary constraints to the virus, Figure 2 . A simplified view of some events involved in RNA virus transmission, that takes into consideration that RNA viruses are quasispecies (mutant distributions). A swine-human transmission is used as illustration. An RNA virus replicates in an infected swine and it can shed different amounts of virus (a, b, c) that can reach a susceptible human. If two specific mutations are needed for the virus to initiate replication in the exposed human host, only the mutant spectrum that includes the required mutations will be established in the human host (in this case distribution b). If viral replication continues in the same individual (human figure on the right, two time points of the same human depicted as separated by the grey arrow), a new mutant distribution will be generated, shaped by the selective constraints imposed by each individual human (immune response and others). Human-to-human transmission (not shown in this scheme) will again involve bottlenecks of different intensities (number of genomes that reach the successive recipient humans). When transmissions occur among individuals of the same host species, it is likely that most mutant distributions will include genomes that are replication-competent in the recipient host. The picture is in reality more complex, as documented in the text. However, the scheme emphasizes the fact that viruses are not defined sequences but mutant distributions, and very frequently this pro-adaptive population structure has not been considered in treatments of emerging viral infections.