Microscopy pictures of human stem cell-derived mini coronary heart organoids. The left panel reveals wholesome, beating coronary heart cells, whereas the suitable panel reveals tissue contaminated with hantavirus (pink), which disrupted cell construction and stopped the organoid’s heartbeat. Credit score: Arjit Vijey Jeyachandra / Arumugaswami lab
UCLA researchers have created miniature stem cell-based organoid fashions of human lungs, hearts and brains to check how hantaviruses—uncommon however usually lethal viruses unfold by rodents—infect the physique. Hantaviruses have been thrust into the nationwide highlight earlier this 12 months as the reason for demise for Betsy Arakawa, the classical pianist and spouse of late actor Gene Hackman.
The researchers’ findings, printed in PLOS Pathogens, present how the Andes virus, the one hantavirus recognized to unfold from individual to individual, infects a variety of tissues. The researchers additionally recognized promising compounds that blocked the virus in lab checks, providing hope for future therapies.
Hantaviruses have been a worldwide well being concern because the Nineteen Fifties, once they prompted hundreds of circumstances of hemorrhagic fever in the course of the Korean Conflict. Right this moment, they proceed to trigger sporadic outbreaks world wide, with mortality charges starting from 1% to 40%, relying on the pressure of the virus.
Within the U.S., Sin Nombre virus has prompted circumstances of extreme respiratory sickness, whereas Previous World Hantaan virus is understood for inflicting kidney illness in Asia. Scientists are significantly frightened concerning the Andes virus, present in South America, as a result of it’s the first hantavirus recognized to unfold between individuals. Latest deaths in New Mexico and California have underscored the continuing danger these viruses current.
“Hantaviruses pose a serious threat to public health, yet we know little about how they attack the human body,” mentioned Dr. Vaithi Arumugaswami, senior writer of the brand new examine and a member of the Eli and Edythe Broad Heart of Regenerative Drugs and Stem Cell Analysis at UCLA. “By creating human organoid systems, we can finally see how these viruses behave in lung, heart and brain tissue—and start to identify ways to stop them.”
Finding out an infection with organoids
Scientists depend on animal fashions—normally hamsters—to check how viral infections unfold all through entire organ programs. However the excessive infectiousness of hantaviruses, mixed with the necessity for biosafety stage 4 containment, makes it very troublesome to check their systemic results in animals. To beat this, the UCLA-led crew used human stem cells to develop organoids—3D mini-organs that mimic the construction and performance of human tissues.
The crew uncovered these organoid fashions to 3 hantaviruses, Andes virus, Hantaan virus and Sin Nombre virus, to see how every contaminated the completely different organs. The variations have been putting.
The Andes virus contaminated all cell sorts examined—lung epithelial and endothelial cells, cardiomyocytes and astrocytes—whereas the Hantaan virus contaminated coronary heart and mind cells extra selectively, and Sin Nombre virus largely remained confined to lung endothelial cells.
“This is the first evidence that Andes virus can replicate efficiently in human lung organoids,” mentioned Arunachalam Ramaiah, co-senior writer of the brand new examine. “It shows just how versatile—and dangerous—this virus can be.”
The researchers additionally found that Andes virus disrupts mobile metabolism in alarming methods. In lung cells, the virus triggered irritation and cell harm whereas shutting down ldl cholesterol and fat-processing pathways. In coronary heart organoids, the virus disrupted cell construction and stopped the guts cells from beating rhythmically.
“The virus reprograms cell metabolism to favor its own survival,” mentioned Arumugaswami, who can be a professor of molecular and medical pharmacology at UCLA. “That disruption may contribute to the severe lung and heart damage seen in patients.”
Promising antiviral drug candidates
There are not any presently accredited therapies or extensively out there vaccines for hantaviruses. To handle this hole, the researchers examined a panel of potential medication on their human cell mannequin system.
They discovered that urolithin B—a pure compound present in sure fruits and nuts—strongly inhibited Andes virus an infection. The compound additionally restored regular metabolism in contaminated cells whereas leaving wholesome cells largely unchanged. One other compound, the antiviral medicine favipiravir, already accredited in Japan to deal with influenza, additionally blocked the virus.
“Two compounds, urolithin B and favipiravir, showed real promise in blocking Andes virus,” mentioned Nikhil Chakravarty, a co-author and medical scholar at California College of Science and Drugs. “It’s early work, but it points us toward the possibility of new therapies where none currently exist.”
Though hantavirus infections stay comparatively uncommon within the U.S., warming temperatures and habitat shifts might enhance dangers as rodents search shelter in additional human-occupied areas.
“The impacts of climate change may bring people into more frequent contact with hantavirus carriers,” mentioned Arjit Vijey Jeyachandran, first writer and a bioinformatics programmer on the David Geffen College of Drugs at UCLA. “That makes it even more important to understand how these viruses spread—and how we can stop them.”
Further authors embrace Joseph Ignatius Irudayam, Swati Dubey, Maria Daskou, Anne Zaiss, Gustavo Garcia Jr., Bindu Konda, Aayushi Shah, Aditi Venkatraman, Baolong Su, Cheng Wang, Qi Cui, Kevin Williams, Sonal Srikanth, Ashok Kumar, Yanhong Shi, Dr. Arjun Deb, Robert Damoiseaux and Barry Stripp.
Extra data:
Arjit Vijey Jeyachandran et al, Differential tropisms of outdated and new world hantaviruses affect virulence and growing host-directed antiviral candidates, PLOS Pathogens (2025). DOI: 10.1371/journal.ppat.1013401
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Mini-organ fashions reveal hantavirus secrets and techniques, level to therapies (2025, August 26)
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