Passage-attenuated Powassan virus LI9P protects mice from lethal LI9 challenge and links envelope residue D308 to neurovirulence.

ABSTRACT: Powassan virus (POWV) is an emergent tick-borne flavivirus that causes lethal encephalitic disease and chronic neurologic deficits in surviving patients. POWV-LI9 is a tick-derived isolate that causes neurovirulent disease and age-dependent lethality in mice. Serial passage of VeroE6 cells infected with LI9 resulted in eight amino acid changes in a POWV strain LI9P. LI9P fails to cause neurological sequelae, or lethality in C57BL/6 mice yet elicits neutralizing POWV antibody responses and protects mice from lethal LI9 challenge. Analysis revealed that LI9, but not LI9P, is present at high levels in the CNS, suggesting that LI9P is restricted from neuroinvasion or CNS replication. LI9 and LI9P are distinguished by a D308N envelope change within a domain associated with cell attachment. We e

SUBMITTER: Himmler GE 

PROVIDER: S-EPMC11980571 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature