Within-Host Genetic Diversity of Endemic and Emerging Parvoviruses of Dogs and Cats

Abstract

Viral emergence can result from the adaptation of endemic pathogens to new or altered host environments, a process that is strongly influenced by the underlying sequence diversity. To determine the extent and structure of intrahost genetic diversity in a recently emerged single-stranded DNA virus, we analyzed viral population structures during natural infections of animals with canine parvovirus (CPV) or its ancestor, feline panleukopenia virus (FPV). We compared infections that occurred shortly after CPV emerged with more recent infections and examined the population structure of CPV after experimental cross-species transmission to cats. Infections with CPV and FPV showed limited genetic diversity regardless of the analyzed host tissue or year of isolation. Coinfections with genetically distinct viral strains were detected in some cases, and rearranged genomes were seen in both FPV and CPV. The sporadic presence of some sequences with multiple mutations suggested the occurrence of either particularly error-prone viral replication or coinfection by more distantly related strains. Finally, some potentially organ-specific host effects were seen during experimental cross-species transmission, with many of the mutations located in the nonstructural protein NS2. These included residues with evidence of positive selection at the population level, which is compatible with a role of this protein in host adaptation.Emerging viruses that gain new host ranges are major threats to human and animal health. However, the evolutionary mechanisms that allow viruses to infect new hosts and establish self-sustaining transmission chains are complex and far from understood. In most cases studied to date, several mutations together determine the new host range, but where, when, and how these mutations arise have remained largely enigmatic. Many cases of viral emergence probably represent multistage adaptations to an altered host environment, where the initial emerging virus is poorly adapted to the recipient host and causes only inefficient transmission. Further mutations are then required for complete adaptation to the new host. The success of the new pathogen is therefore likely to be highly influenced by the genetic diversity of the viral population, with more variable viral populations being particularly prone to generating successful emerging infections.The extent of genetic diversity present within viral populations is determined largely by a balance between erroneous replication (measured as the mutation rate) and purifying selection (reflected in the population substitution rate, defined as the number of fixed mutations/nucleotide site/year), with particularly high error rates in RNA viruses that replicate using RNA-dependent RNA polymerases (15), or, in the case of retroviruses, reverse transcriptases. Although large doublestranded DNA viruses possess mutation rates far lower than those seen in RNA viruses, some small single-stranded DNA

Molecular Characterization of Infectious Clones of the Minute Virus of Canines Reveals Unique Features of Bocaviruses

“…NS2 knockout mutants in the infectious clone of CPV show no obvious differences in viral DNA replication in cell culture or in dogs (65). However, recent studies examining the within-host genetic diversity of CPV infection showed that NS2 might play a role in host adaptation of CPV (30). MVM NS2 is a multifunctional protein; it also has a role in ssDNA production, capsid assembly, and nuclear export of virions (16,24,43,45,55).…”

Canine parvovirus 2c infection in a cat with severe clinical disease

“…However, the evolutionary mechanisms that allow this virus to infect new hosts and the emergence of new strains in "real time" are complex and not yet understood. 15 The new variants of CPV appear to be able to infect cats and other hosts (puma, coyote, gray wolf, bobcat, raccoon, and striped skink) because the variants can bind the feline transferrin receptor as well as the receptors of other hosts, 1,16 while still remaining a severe threat to dogs. The role of these variants in cats still remains somewhat uncertain.…”

Recent host-shifts in ranaviruses: signatures of positive selection in the viral genome

“…For instance, parvoviruses experienced adaptive evolution of the gene encoding the surface-exposed viral protein, the capsid, after this virus first became established in dogs in the 1970s (Hoelzer et al, 2008). These evolutionary changes improved the interaction between the capsid and the dog-encoded cell-surface receptor for virus entry, the transferrin receptor.…”

“…Computational tools that can detect episodes of rapid adaptation of specific genes, in conjunction with the increased availability of genomic data, have provided new avenues for identifying candidate genes potentially involved in dynamic processes such as host switching (Sawyer & Elde, 2012). In many cases, genes that are involved in host-pathogen interactions exhibit episodes of intense positive selection during the process of establishing a new host species (Shackelton et al, 2005;Hoelzer et al, 2008;Meyerson & Sawyer, 2011;Bhatt et al, 2013). Genes identified via these methods are often involved in immune evasion, replication, reproduction, gene expression, host-pathogen co-evolution and host defences (Endo et al, 1996;Yang et al, 2000;McLysaght et al, 2003;Harrison & Bonning, 2004;Shackelton et al, 2005;Sabeti et al, 2006;Kosiol et al, 2008;Elde et al, 2012).…”