A key topic for us has been to understand the fundamental controls of host range of viruses. The models we have been examining for many years include canine parvovirus (CPV) and the comparison of the virus with feline panleukopenia virus (FPV). More recently we are also looking at the sequence variation of the equine and canine influenza viruses.
Parvovirus Host Range
We are examining in detail the capsid sequences and structures that determine the ability of the CPV to infect dog cells, while the FPV cannot infect those cells. The canine TfR is a key player in this infection process. Mavis Agbandje-McKenna, at the University of Florida in Gainesville, and with Susan Hafenstein’s laboratory at Penn State University.Capsids of both CPV and FPV can bind the transferrin receptor (TfR) on feline cells, while only CPV strains bind to the canine TfR. Introducing two CPV-derived changes of VP2 residues 93 and 323 into the capsid of FPV extended the host range of that virus and allowed it to bind and infect canine cells. Those residues together controlled canine TfR binding of the capsids, although neither change alone gave significant levels of binding. In CPV the reciprocal mutants caused the ability to infect canine cells to be lost only when the two residues were changed together to the FPV sequences. Substitutions of VP2 residue 93 in CPV with several other amino acid residues, or a changing of residue 323 alone reduced the efficiency of canine cell infection, but those had only a moderate effect on canine cell infection and the canine TfR binding. In addition to the receptor binding, other differences between the viruses likely have smaller but nonetheless critical. These studies are being conducted in collaboration with the laboratory of
Canine influenza virus
Another host range switch is that of the equine influenza to dogs. Here we are interested particularly in the evolutionary events that allowed the virus to change its host range to establish a self-sustaining epidemic in the new host, and the subsequent changes that allowed it to propagate in the dogs. The nature of the emergence and spread allows models to be developed for the host and immune pressures, while the geographic movement and separation of different virus lineages may allow us to define the critical events in the virus emergence.
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Callaway, H.M., Welsch, K., Weichert, W., Allison, A.B., Hafenstein, S.L., Huang, K., Iketani, S., Parrish, C.R. (2018). Complex and dynamic interactions between parvovirus capsids, transferrin receptors and antibodies control cell infection and host range. Journal of Virology, 92 no. 13 e00460-18
Wasik, B.R., Barnard, K.N., Ossiboff, R.J., Khedri, Z., Feng, F.H., Yu, H., Chen, X., Perez, D.R., Varki, A., Parrish, C.R. (2017). Distribution of O-acetylated sialic acids among target host tissues for influenza virus. mSphere 2 (5), e00379-16
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.
Parrish, C.R., Kawaoka, Y. (2005). The origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza A viruses. Annual Review of Microbiology 59:553-586.
Hueffer, K., Palermo, L.M., Parrish, C.R. (2004). Parvovirus infection of cells using variants of the feline transferrin receptor altering clathrin-mediated endocytosis, membrane domain localization and capsid binding domains. Journal of Virology 78: 5601-5611.
Hueffer, K., Parker, J.S.L., Weichert, W.S., Geisel, R.E., Sgro, J-Y., Parrish, C.R. (2003). The natural host range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferrin receptor and other receptors. Journal of Virology 77:1718-1726.
Govindasamy, L., Hueffer, K, Parrish, C.R., Agbandje-McKenna, M. (2003). The structures of host range controlling regions of the capsids of canine and feline parvoviruses and mutants. Journal of Virology. 77:12211-12221.
Hueffer, K, Govindasamy, L., Agbandje-McKenna, M., Parrish, C.R. (2003). Combinations of two capsid regions controlling canine host range determine canine transferrin receptor binding by canine and feline parvoviruses. Journal of Virology 77: 10099-10105.