Single Mutations in the XXXX 300 Loop Region of the Three-Fold Spike of the Carnivore Parvovirus Capsid Can Determine Host Range.

@entity778 @entity3967 @entity8959 @entity17400 @entity235 @entity69 @entity281 @entity71902 @entity24715 @entity3689 @entity2574
Sylvatic carnivores, such as @entity3967 , have recently been recognized as important hosts in the evolution of @entity24715 ( @entity24715 ), a pandemic pathogen of domestic @entity235 . Although viruses from @entity3967 do not efficiently bind the @entity235 @entity71902 ( @entity71902 ) or infect @entity235 cells, a single mutation changing an @entity2574 to a @entity8959 at capsid ( @entity17400 ) position 300 in the prototype @entity3967 @entity24715 allows @entity235 cell @entity281 . Because @entity17400 position 300 exhibits extensive @entity3689 variation among the carnivore parvoviruses, we further investigated its role in determining host range by analyzing its diversity and evolution in nature and by creating a comprehensive set of @entity17400 position 300 mutants in infectious clones. Notably, some position 300 residues rendered @entity24715 noninfectious for @entity235 , but not cat or fox, cells. Changes of adjacent residues (residues 299 and 301) were also observed often after cell culture passage in different hosts, and some of the mutations mimicked changes seen in viruses recovered from natural infections of alternative hosts, suggesting that compensatory mutations were selected to accommodate the new residue at position 300. Analysis of the TfRs of carnivore hosts used in the experimental evolution studies demonstrated that their glycosylation patterns varied, including a glycan present only on the domestic @entity235 @entity71902 that dictates susceptibility to parvoviruses. Overall, there were significant differences in the abilities of viruses with alternative position 300 residues to bind TfRs and infect different carnivore hosts, demonstrating that the process of @entity281 is highly host dependent and that @entity17400 position 300 is a key determinant of host range. IMPORTANCE: Although the emergence and pandemic spread of @entity24715 ( @entity24715 ) are well documented, the carnivore hosts and evolutionary pathways involved in its emergence remain enigmatic. We recently demonstrated that a region in the capsid structure of @entity24715 , centered around @entity17400 position 300, varies after transfer to alternative carnivore hosts and may allow @entity281 of previously nonsusceptible hosts in vitro. Here we show that @entity17400 position 300 is the most variable residue in the parvovirus capsid in nature, suggesting that it is a critical determinant in the cross-species transfer of viruses between different carnivores due to its interactions with the @entity69 receptor to mediate @entity281 . To this end, we demonstrated that there are substantial differences in receptor binding and infectivity of various @entity17400 position 300 mutants for different carnivore species and that single mutations in this region can influence whether a host is susceptible or refractory to @entity778 .
