Advanced Cryo-EM Technique Reveals High-Resolution Structure of Powassan Virus

As summer approaches, the increased outdoor activities raise public awareness about ticks and the diseases they transmit. One of the most concerning tick-borne viruses in North America is the Powassan virus (POWV), which has been linked to severe neurological conditions, including encephalitis and paralysis. Recent research led by a team from Penn State University, in collaboration with the University of Minnesota and the U.S. Department of Agriculture, has successfully utilized cryo-electron microscopy (cryo-EM) to elucidate the high-resolution 3D structure of POWV, a key step in developing effective treatments and prevention strategies. The study was published on July 9, 2025, in the journal Science Advances.

The Powassan virus, a member of the Flaviviridae family, has seen an increase in infection rates over recent years, with no specific treatments currently available. According to Joyce Jose, Associate Professor of Biochemistry and Molecular Biology at Penn State, understanding the virus's structure is crucial for developing therapeutic approaches. "We don't know much about the structure of this virus, but we need to know the structure in order to come up with strategies to treat and prevent infection," said Jose.

The research team faced challenges in studying POWV due to its pathogenic nature, which often requires inactivation methods that can damage the virus. To overcome this, the researchers employed a surrogate model using a modified yellow fever vaccine virus, creating a chimeric virus that replicated the surface proteins of POWV. This innovative approach enabled the team to accurately visualize the virus structure without the inherent risks associated with studying the live POWV.

Using the advanced capabilities of cryo-EM, the researchers captured the intricate arrangement of the virus's surface proteins, specifically the envelope and membrane proteins, which are crucial for viral entry into host cells. The study revealed a herringbone-like pattern of these proteins, providing insights into how the virus interacts with its vectors and hosts.

"With cryo-EM, we can see every molecule in the virus, enabling us to reconstruct a detailed 3D structure," Jose explained. This detailed visualization aids in understanding the transmission dynamics of the virus. Interestingly, the research indicated that the transmission capabilities of the virus are not determined by the structural proteins, but rather by nonstructural proteins, highlighting the complexity of virus-vector interactions.

The implications of this research extend beyond basic virology; understanding the structure of POWV could inform the development of vaccines and therapeutics that target surface proteins, essential for the virus's lifecycle. As noted by Susan Hafenstein, Senior Author and researcher at the University of Minnesota, this knowledge is pivotal for devising strategies to mitigate the risks associated with emerging tick-borne diseases.

The research was supported by funding from the National Institutes of Health and the U.S. Department of Agriculture. The findings underscore the necessity of continued research in viral structure and transmission to address public health concerns posed by tick-borne diseases. As the team plans further investigations into the factors influencing viral transmission, the insights gained from this study stand to contribute significantly to the field of infectious diseases and public health.

For those interested in the ongoing evolution of tick-borne viruses and the scientific advancements in understanding their structures, this study serves as a pivotal reference point. The increasing prevalence of ticks in new regions necessitates ongoing vigilance and research to protect public health effectively.