Phylogeographic Analysis Of Pseudogymnoascus Destructans Partitivirus-Pa Explains The Spread Dynamics Of White-Nose Syndrome In North America

Understanding the dynamics of white-nose syndrome spread in time and space is an important component for the disease epidemiology and control. We reported earlier that a novel partitivirus, Pseudogymnoascus destructans partitivirus-pa, had infected the North American isolates of Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome in bats. We showed that the diversity of the viral coat protein sequences is correlated to their geographical origin. Here we hypothesize that the geographical adaptation of the virus could be used as a proxy to characterize the spread of white-nose syndrome. We used over 100 virus isolates from diverse locations in North America and applied the phylogeographic analysis tool BEAST to characterize the spread of the disease. The strict clock phylogeographic analysis under the coalescent model in BEAST showed a patchy spread pattern of white-nose syndrome driven from a few source locations including Connecticut, New York, West Virginia, and Kentucky. The source states had significant support in the maximum clade credibility tree and Bayesian stochastic search variable selection analysis. Although the geographic origin of the virus is not definite, it is likely the virus infected the fungus prior to the spread of white-nose syndrome in North America. We also inferred from the BEAST analysis that the recent long-distance spread of the fungus to Washington had its root in Kentucky, likely from the Mammoth cave area and most probably mediated by a human. The time to the most recent common ancestor of the virus is estimated somewhere between the late 1990s to early 2000s. We found the mean substitution rate of 2 X 10(-3) substitutions per site per year for the virus which is higher than expected given the persistent lifestyle of the virus, and the stamping-machine mode of replication. Our approach of using the virus as a proxy to understand the spread of white-nose syndrome could be an important tool for the study and management of other infectious diseases.Author summaryWhite-nose syndrome is a deadly fungal disease of North American bats, that has been spreading from the northeastern United States to Canada and to the south and west. Understanding the spread has been difficult because the fungus is nearly identical throughout North America, consistent with a recent introduction. The fungus is infected with an RNA virus that shows significant variation over time, especially in the gene for the coat protein. Here we used the variation in the virus to create a phylogenetic tree that could help us understand the spread of the fungal disease. We found that the fungus/virus combination was likely in North America since around 1999, earlier than previously thought. In addition, we found that the initial site of introduction was more likely Connecticut, rather than New York State, and that the recently identified fungal infections in bats in Washington state most likely came from Kentucky. This study also demonstrates that viruses of a pathogen can be used to understand the epidemiology of the pathogen.