Parvovirus variation for disease: a difference with RNA viruses?

Abstract

The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high genetic heterogeneity and large population sizes resembling the quasispecies found in RNA viruses. These viruses multiply in proliferating cells, causing acute, persistent or latent infections relying in the immunocompetence and developmental stage of the hosts. Some parvovirus populations in natural settings, such as carnivore autonomous parvoviruses or primate adeno associated virus, show a high degree of genetic heterogeneity. However, other parvoviruses such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show little genetic variation, indicating different virus-host relationships. The Parvoviridae evolutionary potential in mammal infections has been modeled in the experimental system formed by the immunodeficient scid mouse infected by the minute virus of mice (MVM) under distinct immune and adaptive pressures. The sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic populations present in the organs of 26 mice showed consensus sequences not representing the complex distribution of viral clones and a high genetic heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt accumulated over 2-3 months). Specific amino acid changes, selected at a rate up to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses with new tropism and increased fitness. Further molecular analysis supported the notion that, in addition to immune pressures, the affinity of molecular interactions with cellular targets, as the Crml nuclear export receptor or the primary capsid receptor, as well as the adaptation to tissues enriched in proliferating cells, are major selective factors in the rapid parvovirus evolutionary dynamics.