Virus Evolution

Emergence and Evolution of Canine Parvovirus, H3N8 Canine Influenza Virus, and H3N2 Canine Influenza Virus as New Epidemic Viruses.

We are examining the evolution of CPV and its ancestor feline paneleukopenia virus (FPV), and also canine influenza virus (CIV) and its ancestor equine influenza virus (EIV). CPV emerged in 1978 in dogs through the introduction of a single ancestral virus, and in the past 30 years the viruses have continued to evolve while we have studied them. Most recently this project has been carried out by Ian Voorhees and Brian Wasik in the laboratory. We have collaborated with a number of other groups in these studies, in particular with the group of Eddie Holmes in the Charles Perkins Centre, University of Sydney. In the influenza studies we are also collaborating with Pablo Murcia at the University of Glasgow and Centre for Virus Research. Our main focus is to understand the molecular determinants of viral emergence through an integrative approach combining tools from molecular virology, epidemiology and population biology.

The general evolutionary mechanisms that give rise to emerging viruses in new hosts are still poorly understood, but clearly dependi on the virus, host and epidemiologic scenario involved. Most viral emergence events involve multiple stages including exposure and transfer of the virus to the new host (“spill over”), followed by adaptations to the new host environment. 

Phylogeny_CPV

Phylogeny showing the relationships between FPV-like viruses, and the CPV-like viruses. The CPV isolates are divided into two types, the original 1978 strain termed CPV type-2 (blue), and the more recent strain termed CPV-2a (cyan).

We are studying three model systems – two strains of canine influenza virus (CIV) (H3N8 and H3N2), as well as the canine parvovirus (CPV). CPV is a recently emerged virus that derived from a single common ancestral sequence. This single stranded DNA (ssDNA) virus emerged in the 1970s and underwent two host-range changes. The donor virus sequence has not been identified, but phylogenetic evidence points towards a virus related to a parvovirus of an unidentified carnivore. After circulating undetected in the European dog population for some time, CPV spread globally as a new pathogen of dogs. This virus (CPV type-2) was unable to infect cats, but underwent what appears to have been a selective sweep within a year, and the newly arising strain (CPV type-2a) readily infected cats. Natural infections of cats with CPV have been reported, but these appear to represent single transmission events, and FPV has remained the more prevalent parvovirus of cats. Host range restrictions have been mapped to specific residues on the viral capsid, and the mutations that provide the feline host range of CPV-2a are different from the residues determining the feline host range of FPV, indicating a compensatory nature of these host-range mutations.

The H3N8 strain of CIV emerged around 2000 in the United States from an endemic virus of horses, the H3N8 equine influenza virus (EIV). CIV was first recognized during an outbreak in racing greyhounds where the virus caused severe hemorrhagic disease with high associated mortality, but has since been causing only mild to subclinical disease. Outbreaks have been reported from clinics and kennels across the US, but the virus appears not to be spreading outside North America. After about 2012 the virus was found only on the Eastern Seabord of the USA, mainly in New York city, and the virus appears to have largely faded out by later 2016.

Publications

Voorhees, I.E.H., Dalziel, B.D., Glaser, A., Dubovi, E.J., Murcia, P.R., Newbury, S., Toohey-Kurth, K., Su, S., Kriti, D., Van Bakel, H., Goodman, L.B., Leutenegger, C., Holmes, E.C., Parrish, C.R. (2018). Multiple incursions and recurrent epidemic fade-out of H3N2 canine influenza A virus in the United States. Journal of Virology, 92. pii: e00323-18.

Hoelzer, K., Shackelton, L.A., Holmes, E.C., Parrish, C.R.. (2008) Within-host genetic diversity of endemic and emerging parvoviruses of dogs and cats. Journal of Virology 82:11096-11105

Parrish, C.R., Holmes, E.C., Morens, D., Park, E-C., Burke, D., Calisher, C., Saif, L., Daszak, P. (2008).  Cross-species transmission and the emergence of new epidemic diseases. Microbiology and Molecular Biology Reviews. 2008 72:457-470.

Hoelzer, K.; Shackleton, L.A. and Parrish, C.R. (2008). Presence and roles of cytosine methylation in DNA viruses of animals. Nucleic Acids Res. 36:2825-2837.

Hoelzer, K., Shackelton, L.A., Parrish, C.R. Holmes, E.C. (2008). Phylogenetic analysis reveals the emergence, evolution and dispersal of carnivore parvoviruses. Journal of General Virology 89:2280-2289

Hoelzer, K., Parrish C.R. (2008). Evolution and variation of the parvoviruses. Chapt. 17. In: Origin and Evolution of Viruses, 2nd Edn. (Eds. Domingo, E. Holland, J., Parrish, C.R.). Elsevier. pp 393-416.

Shackelton, L.A., Hoelzer, K., Parrish, C.R., and Holmes, E.C. (2007). Comparative analysis reveals frequent recombination in the parvoviruses. Journal of General Virology 88:3294-3301.

Shackelton, L.A., Parrish, C.R., Truyen, U., Holmes, E.C. (2005) High rate of viral evolution associated with the emergence of carnivore parvovirus. Proceedings of the National Academy of Science. (USA) 102: 379-384.

Badgett, M.R., Auer, A., Carmichael, L.E., Parrish, C.R., and Bull, J.J. (2002) Evolutionary dynamics of a viral attenuation. Journal of Virology 76:10524-10529.

Truyen, U., Evermann, J. F., Vieler, E., and Parrish, C. R. (1996). Evolution of canine parvovirus involved loss and gain of feline host range. Virology 215:186-189.

Truyen, U., Gruenberg, A., Chang, S. F., Obermaier, B., Veijalainen, P., and Parrish, C. R. (1995). Evolution of the feline-subgroup parvoviruses and the control of canine host range in vivo. Journal of Virology 69:4702-4710.