Understanding the next Ebola virus rather than panicking about the current one

Parvovirus Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. This is an important example of a viral pathogen that evolved by cross-species transmission and mutation to initiate a disease pandemic, something virologists have been writing about for years but is now highly fashionable (think: Ebola: Will ebola come to the UK? Yes. And will it kill us all? No).

Carnivore parvoviruses infect many species, and their passage in different hosts may select mutations that facilitate host jumping; for example, natural passage of CPV in raccoons may have facilitated its adaptation to dogs. A new papers demonstrates that these barriers can be overcome by only a few mutations in the virus that probably alter host receptor binding, and that host adaptation can differ dramatically among very similar viruses.

Passage of viruses in cell cultures of different hosts results in mutations at the same sites that vary in nature and confer fitness increases, strongly suggesting that they are adaptively important. This shows that parvoviruses may cross species barriers to infect less susceptible hosts through single or only a few mutations, and that differences in the genetic background, host range, and/or evolutionary history of the viruses influence their propensity to jump hosts. These discoveries help reveal the mechanisms that control host switching and virus emergence.

Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species. (2014) PLoS Pathog 10(11): e1004475. doi:10.1371/journal.ppat.1004475
Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of virus sequences recovered from different wild carnivore species, as shown here, demonstrated that 95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range.

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One Response to Understanding the next Ebola virus rather than panicking about the current one

  1. rybicki says:

    Canine circovirus, anyone? That is – if it exists….

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