Hantaviruses, notorious for their high mortality rate of nearly 40%, have long been a global health concern due to the absence of approved vaccines or treatments. These viruses, transmitted from rodents to humans, gained notoriety in the United States when Betsy Arakawa, wife of actor Gene Hackman, succumbed to a hantavirus infection in New Mexico last year. Now, a groundbreaking study published in the journal Cell has unveiled a detailed molecular map of the Andes virus, a hantavirus prevalent in the southwestern U.S. and parts of North and South America. This discovery marks a significant stride toward developing vaccines and antibody therapies.
Researchers from The University of Texas at Austin have meticulously crafted a high-resolution blueprint of a protein complex used by the Andes virus to invade host cells. This 3D map, showcasing molecular shapes at the nanoscale, is pivotal for vaccine development and antibody therapy creation. The study’s findings enabled the team to produce a vaccine candidate that triggered the production of neutralizing antibodies against the Andes virus in mice.
Mapping the Virus: A New Frontier
The research, led by Jason McLellan, a professor of molecular biosciences at UT Austin, and Luqiang Guo, a postdoctoral fellow, was partially funded by the National Institutes of Health (NIH), the Welch Foundation, and the Cancer Prevention and Research Institute of Texas. The team focused on the Andes virus’s surface protein complex, known as a Gn-Gc tetramer, which resembles a mushroom-shaped structure. To map these 3D structures, virus-like particles were created to mimic the virus without its infectious genome.
Utilizing a cryo-electron microscope, the researchers reconstructed the Gn-Gc tetramers’ structures by shining an electron beam through a frozen sample to detect molecular shadows. This innovative approach allowed them to achieve an unprecedented resolution of 2.3 angstroms, capturing atomic-level details. This advancement significantly improves upon a previous model with a resolution of 12 angstroms, which had notable inaccuracies.
“People will start to apply this method to many other viruses,” predicted McLellan.
Implications for Vaccine and Therapy Development
The newly revealed structures depict the Gn-Gc tetramer before cell infection, a critical stage for effective vaccines and antibody therapies. Surface proteins alter post-infection, necessitating the development of stabilizing mutations to lock these proteins in their pre-infection state. The team plans to leverage artificial intelligence to identify suitable mutations, enhancing the efficacy of future vaccines.
In 2024, the NIH highlighted several virus families, including hantaviruses, as particularly dangerous due to the lack of effective vaccines or treatments, underscoring their pandemic potential. The NIH’s ReVAMPP program awarded grants to study these viruses and develop countermeasures, supporting the Provident consortium’s research efforts. This consortium, led by McLellan and Kartik Chandran from Albert Einstein College of Medicine, aims to address other high-risk viruses like measles and Nipah virus.
Collaborative Efforts and Future Directions
The study was a collaborative effort involving researchers from Texas A&M University, The University of Texas Southwestern Medical Center, and HDT Bio in Seattle. Key contributors included Zunlong Ke, an assistant professor of molecular biosciences, and Elizabeth McFadden, a graduate student in cell and molecular biology at UT Austin.
As the scientific community continues to explore the potential of this new mapping technique, the implications for combating hantaviruses and other viral threats are profound. The detailed structural insights gained from this research pave the way for innovative solutions to prevent future outbreaks and enhance global pandemic preparedness.
Looking ahead, the research team is poised to refine their vaccine candidates and explore additional stabilizing mutations, with the ultimate goal of developing robust therapies to combat hantaviruses and mitigate their impact on public health.
