Just months after a deadly Andes hantavirus outbreak aboard a cruise ship captured international attention, researchers at LSU Health Shreveport are helping to answer one of the biggest remaining questions about how the virus infects people. In a new study published in Nature, scientists at LSU Health Shreveport alongside collaborators from Albert Einstein College of Medicine, Bronx, NY and Institut Pasteur, Paris, show how the virus recognizes its target on a human cell, a finding that could lead to effective therapies against Andes virus and other hantaviruses.
The publication features significant contributions from LSU Health Shreveport researchers including co-first author Ramandeep Kaur, PhD, Postdoctoral Fellow in Microbiology and Immunology; Rohit K. Jangra, PhD, Assistant Professor of Microbiology and Immunology; Lohit Khera, PhD, a former Postdoctoral Fellow in Microbiology and Immunology; Upendra P. Lambe, PhD, Postdoctoral Fellow in Microbiology and Immunology; Jian Wang, PhD, Assistant Core Director of the Bioinformatics and Modeling Core within the Center for Applied Immunology and Pathological Processes (CAIPP); and Rona S. Scott, PhD, Core Director of the CAIPP Bioinformatics and Modeling Core.
The hantavirus outbreak aboard a cruise ship sickened passengers and claimed lives, reminding the world that these rare but deadly viruses remain a serious public health threat. While hantavirus infections are uncommon, severe cases can be fatal and there are currently no approved therapies specifically designed to treat them.
“Hantaviruses are carried by rodents and can cause devastating illness in humans,” said Dr. Rohit Jangra, assistant professor of microbiology and immunology at LSU Health Shreveport. “People become infected accidentally, and once the virus gets into our cells, it can make us extremely sick. To stop these viruses, we first must understand exactly how they get inside.”
The research teams focused on understanding how Andes hantavirus attaches to a protein on the surface of human cells known as PCDH1. Scientists have long known this protein acts as a critical entry point for the virus, but until now they did not understand precisely how the interaction occurred.
Using advanced structural imaging techniques, researchers created a detailed molecular picture showing how the virus recognizes and binds to the receptor. The findings reveal a previously unknown binding pocket that allows the virus to gain access to cells while helping it evade parts of the immune response.
“The depth of this pocket helps explain how the virus limits antibody access,” Jangra said. “What’s striking is how the same pocket can accommodate the receptor while restricting antibody access. PCDH1’s long, slender shape lets it reach deep inside, but most antibodies are too bulky to follow.”
LSU Health Shreveport researchers played a critical role in validating the discoveries made by the international team. Over the past several years, Jangra’s laboratory has developed innovative systems that allow scientists to safely study highly dangerous viruses without working directly with infectious hantavirus.
“We developed a safer research system that allows us to study how the virus and the receptor interact at a molecular level,” Jangra said. “Using that system, we were able to make precise changes to the viral proteins and identify which parts were absolutely required for the virus to latch onto the receptor.”
The LSU Health Shreveport team’s findings closely matched the structural observations made by researchers at Institut Pasteur, helping confirm the exact portions of the virus responsible for engaging the receptor.
“This was truly a collaborative effort,” Jangra said. “Scientists in Paris generated detailed structural images. Our team here in Shreveport tested how the virus behaves when specific changes are introduced. Researchers in New York then validated those findings using function experiments. It really took a village to solve this problem.”
While the research does not immediately produce a new drug or vaccine, it provides critical information that could eventually lead to both. By identifying exactly how the virus gains entry into human cells, scientists now have a potential target for future antiviral therapies designed to block infection before it can begin.
“If you want to be a great mechanic, you first have to understand how the engine works,” Jangra said. “The same idea applies here. Before we can stop these viruses, we have to understand the basic mechanisms they use to infect us. That’s what this research is helping us do.”
For Jangra, the study represents another step toward a larger goal: understanding how viruses with only a handful of proteins can outmaneuver the human immune system and cause life-threatening disease.
“The more we learn about how these viruses operate, the better prepared we’ll be for whatever comes next,” he said. “Whether it’s hantavirus or another emerging virus in the future, understanding the basic science is what ultimately helps us protect people.”
The title of the paper is “Structural basis for protocadherin-1 recognition by New World hantaviruses.” Co-authors are: Katik Chandran, PhD, Megan M. Slough, PhD, Albert Einstein College of Medicine; Pablo Guardado-Calvo, Phd, Leandro Battini, PhD, Institut Pasteur; and Ramandeep Kaur, PhD, LSU Health Shreveport. Additional authors are: Alexandra Serris, PhD, Annalisa Meola, PhD, and Felix A. Rey, PhD, Institut Pasteur; Upendra P. Lambe, PhD, Jian Wang, PhD, and Rona Scott, PhD, LSU Health Shreveport; Catalina Florez, PhD, and Nicole M. Joselyn, PhD, The Henry M. Jackson Foundation; Luqiang Guo, PhD, and Jason S. McLellan PhD, The University of Texas at Austin; Gorka Lasso, PhD, University College London; Jose L. Garrido, PhD, (also Universidad San Sebastián) and Raymond Alvarez, PhD, Ichor Biologics LLC; Lohit Khera, Norgen Biotek; Andrew S. Herbert, PhD, U.S. Army Medical Research Institute of Infectious Diseases; Nicole D. Tischler, PhD, (also Fundacion Ciencia & Vida) and Maria I. Barria, PhD, Universidad San Sebastián.
Funding sources include National Institutes of Health: U19AI181977 (“PROVIDENT”) and the European Union (EVH, GAP-101202831)