PROJECT SUMMARY
Powassan virus (family Flaviviridae) is a reemerging tickborne virus endemic in North America and Russia. In
1997, a POWV-like agent was isolated from Ixodes scapularis in New England and determined to be genetically
distinct from the original human isolate. This revealed the existence of two lineages: lineage I, POWV (POWV
L1) and lineage II, deer tick virus (POWV L2). POWV L1 is maintained between I. cookei and woodchucks and
I. marxi and arboreal squirrels, while POWV L2 is maintained in I. scapularis and small mammalian hosts. This
distinction suggests an evolutionary progression of either POWV L1 or L2 into unique transmission cycles and
subsequent adaption to these new hosts. Tick, mammalian, and human isolates from New York State (NYS) are
typically identified as POWV L2, but for the first time in 45 years three POWV L1 isolates were detected including
isolations from I. cookei and the first known isolation of POWV L1 from I. scapularis. Additionally, within the same
timeframe in NYS, POWV L1 was identified in Dermacentor variabilis and POWV L2 in Amblyomma
americanum. With few available isolates, especially POWV L1, little work has been done to elucidate genetic
correlates that confer tick host specificity or the role of tick host responses in driving host-specific adaptation.
Therefore, the goal of this study is to utilize our emergent POWV isolates to understand genetic
correlates of tick host specificity and to investigate the potential for further adaptation to distinct tick
hosts. My previous work suggests introduction of POWV L1 into new tick hosts like I. scapularis facilitates viral
diversification and emergence of host-driven adaptations in proteins involved in immune evasion and replication.
Therefore, I hypothesize introduction of POWV L1 into distinct tick species leads to emergence of tick-specific
substitutions that contribute to increased viral fitness. Additionally, I hypothesize these changes will be tick
specific with distinct adaptation of POWV occurring dependent on tick species. To test this, I propose to:
AIM 1: Investigate the role of tick-driven, emergent substitutions in NS4b on viral fitness using a novel
POWV L1 infectious clone
AIM 2: perform experimental evolution of POWV in distinct tick species: Ixodes scapularis, Dermacentor
variabilis, and Amblyomma americanum to assess changes in viral diversity and describe tick antiviral
responses to POWV
These studies will help further our understanding of POWV adaptation to novel hosts and host-specific, genetic
correlates that influence viral fitness. Additionally, these studies will contribute to the poorly understood tick
antiviral responses to POWV infection. Overall, this work may act as a model for tickborne virus spread and
establishment in new transmission cycles.
