Scientists Reveal How Deadly Andes Hantavirus Attaches to Human Cells

Discovery may help develop treatments for Andes virus and other hantaviruses

BRONX, N.Y., Oct. 21, 2026 /PRNewswire/ -- Earlier this year, an outbreak of Andes hantavirus on a cruise ship, which killed three passengers and sickened 13, highlighted the lack of approved vaccines or treatments for the virus. In a study published today in Nature, scientists at Albert Einstein College of Medicine and collaborators from Institut Pasteur and LSU Health Shreveport 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.

"Eight years ago, we discovered that Andes virus infects human cells by using a particular protein on the cell's surface, called a receptor, but we couldn't figure out exactly how the virus recognized it," said co-corresponding author Kartik Chandran, Ph.D., professor of microbiology and immunology at Einstein. "Our latest work solves this puzzle: We reveal a new way in which a virus can capture its receptor during infection and also suggest how we can fight back with therapies targeted to exploit the resulting viral vulnerability." Dr. Chandran is also the Gertrude and David Feinson Chair in Medicine and the Harold and Muriel Block Faculty Scholar in Virology at Einstein, and a member of Montefiore Einstein Comprehensive Cancer Center.

A Dangerous Virus Family

Hantaviruses are a large family of viruses carried mainly by rodents. They can cause serious and sometimes fatal diseases, including hantavirus pulmonary syndrome, a severe respiratory illness that can rapidly lead to breathing failure. Human infections are mainly caused by inhaling airborne virus particles from infected rodents' urine, droppings, or saliva. Of the more than 20 hantaviruses known to sicken humans, Andes virus is the only one known to spread from person to person, typically through close and prolonged contact. This year's cruise ship outbreak provided a dramatic example of that capability.

The research team had previously shown that, to infect a human cell, the spike protein on the Andes virus surface must latch onto a particular protein, a receptor called PCDH1 on the cell's surface. This receptor essentially serves as a doorway for the virus to enter the cell and then multiply inside it. But an important question remained unanswered: How does the virus's spike protein latch onto PCDH1?

Taking the Picture

Following the discovery of PCDH1 as the Andes virus receptor, the researchers became aware that hantaviruses behave in an unusual way compared to most viruses. For example, the spike protein of SARS-CoV-2, the virus that causes COVID-19, has three identical protein units that come together in a triangle shape. Each unit has a separate part called the receptor-binding domain (RBD) that latches onto its receptor, ACE2. In contrast, the Andes virus spike is an arrangement of four identical protein units locked together into a square. Unlike with SARS-CoV-2 and ACE2, a single protein unit from the Andes virus cannot bind to its receptor; instead, the entire square-shaped spike is needed to capture PCDH1.

As part of their research to focus on what happens at the very beginning of infection when the Andes virus first encounters a human cell, the researchers used cryo-electron microscopy to reveal its structure in sharp detail. That step was accomplished after the team used innovative new methods, including an artificial intelligence-designed scaffold, that enabled the square-shaped Andes virus spike to hold together in a test tube.

"The best way to prove a rare bird exists is to take a picture of it," said Pablo Guardado-Calvo, Ph.D., deputy director of the Virology Department and head of the Structural Biology of Infectious Diseases unit at the Institut Pasteur. "When we mixed this engineered Andes virus spike with PCDH1 and looked at it under the microscope, we knew we had something special."

Find a Pocket, Block it

The structures revealed that a single molecule of PCDH1 embeds itself into the heart of the spike by binding into a deep groove or pocket at its center. The researchers also discovered details on the molecular specifics of the interaction that will be important to design treatments that block it.

"The depth of this pocket also helps explain how the virus limits antibody access," said Rohit Jangra, Ph.D., assistant professor of microbiology and immunology at LSU Health Shreveport. "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."

The team next looked at several antibodies isolated from human hantavirus patients that had previously been shown to block the Andes virus-PCDH1 binding interaction. They found that some of these antibodies could indeed bind close enough to the entrance of the receptor-binding pocket to prevent PCDH1 from entering it; however, they couldn't fit as deeply into the pocket as PCDH1. "This suggests a clever way in which Andes virus can escape receptor-blocking antibodies. The virus mutates so antibodies cannot destroy it, but those changes do not affect its ability to bind to the receptor—a kind of molecular 'friend-or-foe' identification system," Dr. Chandran said.

This strategy that Andes virus evolved to escape antibodies also creates a vulnerability that the team intends to exploit. Although human antibodies are limited to a certain architecture, scientists can create "long and skinny" molecules, suggesting an approach that could block the PCDH1 pocket and offer a blueprint for the development of new antiviral medicines that are urgently needed for Andes virus, and its close relative in the United States and Canada, Sin Nombre virus. "This work creates a unified picture of the hantavirus-receptor interaction that could help us conceive and discover new protective strategies that work broadly against these high-consequence pathogens," said Dr. Guardado-Calvo.

The title of the paper is "Structural basis for protocadherin-1 recognition by New World hantaviruses." Co-authors are: Megan M. Slough, Ph.D., Albert Einstein College of Medicine; Leandro Battini, Ph.D., Institut Pasteur; and Ramandeep Kaur, Ph.D., LSU Health Shreveport. Additional authors are: Alexandra Serris, Ph.D., Annalisa Meola, Ph.D., and Felix A. Rey, Ph.D., Institut Pasteur; Upendra P. Lambe, Ph.D., Jian Wang, Ph.D., and Rona Scott, Ph.D., LSU Health Shreveport; Catalina Florez, Ph.D., and Nicole M. Joselyn, Ph.D., The Henry M. Jackson Foundation; Luqiang Guo, Ph.D., and Jason S. McLellan, Ph.D., The University of Texas at Austin; Gorka Lasso, Ph.D., University College London; Jose L. Garrido, Ph.D., (also Universidad San Sebastián) and Raymond Alvarez, Ph.D., Ichor Biologics LLC; Lohit Khera, Norgen Biotek; Andrew S. Herbert, Ph.D., U.S. Army Medical Research Institute of Infectious Diseases; Nicole D. Tischler, Ph.D., (also Fundacion Ciencia & Vida) and Maria I. Barria, Ph.D., Universidad San Sebastián.

Funding sources include National Institutes of Health: U19AI181977 ("PROVIDENT") and the European Union (EVH, GAP-101202831)

SOURCE Albert Einstein College of Medicine