Atomic-resolution structure of a chimeric Powassan tick-borne flavivirus

Area of Science:

• Virology
• Vaccinology
• Structural Biology

Background:

• Powassan virus (POWV) is an emerging tick-borne flavivirus with increasing incidence in North America.
• The tick vector, *Ixodes scapularis*, is expanding its distribution, leading to more human infections.
• No vaccine or antiviral treatments are currently available for POWV, posing a significant public health risk.

Purpose of the Study:

• To develop a safer alternative for studying POWV, a risk group 3 human pathogen.
• To construct and characterize a chimeric virus using the yellow fever virus vaccine strain 17D (YFV-17D) backbone and POWV structural proteins.

Main Methods:

• Construction of a chimeric virus (yPOWV) using YFV-17D genetic backbone and POWV lineage II external structural proteins.
• Assessment of the chimera's phenotype.
• Determination of the atomic resolution structure of the yPOWV chimera.

Main Results:

• The constructed yPOWV chimera exhibited a phenotype comparable to the wild-type POWV.
• The atomic resolution structure of yPOWV was determined without ambiguity.
• Structural analysis revealed surface glycans and lipid pocket factors.

Conclusions:

• The yPOWV chimera demonstrates potential as a vaccine candidate due to its structural similarities to other flaviviruses and its YFV-17D-like phenotype.
• This chimeric approach offers a safer method for research and potential therapeutic development against POWV infections.