Role of Multiple Hosts in the Cross-Species Transmission and Emergence of a Pandemic Parvovirus

Abstract

Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence.

Canine parvovirus: the worldwide occurrence of antigenic variants

“…The regaining of the feline host range and infection of other hosts is likely to be a selective advantage for the virus (Truyen et al, 1996a). While CPV-2 is considered a host range variant of a virus closely related to FPV that gained the ability to infect dogs via wild carnivores, as previously reported, the emergence of CPV-2a was previously suggested to be due to host adaptation in dogs (Allison et al, 2012). A recent study (Allison et al, 2012) showed that raccoons from the USA have harboured parvoviruses similar to CPV for over 20 years.…”

“…The phylogenetic relationships between CPV-2 isolates from dogs and the viruses from cats (FPV), mink (MEV), raccoon (RPV), raccoon dog (Raccoon dog parvovirus, RDPV) and blue fox (Blue fox parvovirus, BFPV) showed that all CPVs derived from a single common ancestor, and that the strains were mostly similar to viruses from different wildlife animals including raccoons and foxes (Allison et al, 2012(Allison et al, , 2013. CPV was shown to be related to a virus similar to the long recognized FPV, but likely not from cats (Truyen et al, 1995).…”

“…CPV was shown to be related to a virus similar to the long recognized FPV, but likely not from cats (Truyen et al, 1995). CPV-2 likely arose when it acquired mutations that allowed binding to the canine transferrin receptor (TfR) type-1 (Truyen et al, 1996a;Shackelton et al, 2005;Allison et al, 2012). Several studies have demonstrated that the TfR plays a key role in the susceptibility of cells to infection by these viruses (Hueffer et al, 2003;Palermo et al, 2006).…”

“…An additional mutant, 300Asp, of CPV2a/2b has been detected in recent years in domestic or wild felids in southern Asia, as well as in raccoons. The mutation 300Asp is probably the expression of a further adaptation of the virus to replication in the feline or raccoon hosts (Ikeda et al, 2000;Allison et al, 2012).…”

Comparative molecular analysis of strains of the Aleutian Disease Virus isolated from farmed and wild mink

“…Polymorphism in the hypervariable region enables differentiation of strains with varying pathogenicity [12]. The amino acid sequence in this protein may have a significant effect on the range of hosts infected [13], as in the case of CPV-2 [14,15]. The VP2 protein region containing epitopes, due to its significance in pathogenesis as well as its potentially high variability, seems to be a good site in the genome for analysis of polymorphism of the virus in farmed and wild mink populations.…”