Mechanisms of viral emergence

Domingo, Esteban

Viruses generally have multiple genes involved in cellular tropism and host range, that encode non-structural or structural viral proteins [2, 51] . Modification of such genes by mutation or their acquisition by recombination or reassortment opens the way to a change in host range and to disease emergence. In the present article I have emphasized a major issue of RNA virus genetics that has been considered only marginally in several studies on the mechanisms of viral disease emergence. The issue is that RNA viruses replicate as complex mutant distributions, termed viral quasispecies, and that the complexity and composition of mutant distributions are key factors in virus adaptation and persistence [13, 14, 16, 23, 70, 73, 84] (Tab. I). Contrary to designed experiments of adaptation of a virus to new host in which the role of mutant spectra in the adaptation process has been observed [64] , no such observations have been made in the process of a natural emergence. Therefore, there is no definitive proof that a number of related mutants from a donor host reached a potential new host, or that genetic variation of the colonizing virus was essential for the establishment of the virus in the new host. However, what the molecular studies on viral genomes tell us is that when more than one virus particle reaches a recipient host there is a high probability that the genomes will not be identical, and that they may display fitness differences. It is worth noting that fitness changes can occur in viral quasispecies without being reflected in any modification of the genomic consensus nucleotide sequence [30] [31] [32] . Thus, relevant biological information can be lost if surveys of viral genomic sequences (for the purpose of the control of disease emergence or other), are restricted to the determination of consensus sequences. A new era to penetrate into the mutant spectrum composition Vet. Res. (2010) 41:38 has started with the use of the new ultra deep sequencing or microarray-based methodologies by which the characterization of mutant spectra can be based on thousands of sequences [20, 47, 82, 86, 88] .