Key takeaways
- UCLA scientists built miniature models of human lungs, hearts and brains to study hantaviruses, deadly rodent-borne viruses with no current treatments.
- They discovered that Andes virus — the only hantavirus that spreads between people — can infect a wide range of human tissues and disrupt normal cell metabolism.
- The team also identified two existing compounds that blocked the virus in lab tests, offering hope for future therapies.
UCLA researchers have created miniature stem cell-based organoid models of human lungs, hearts and brains to study how hantaviruses — rare but often deadly viruses spread by rodents — infect the body. Hantaviruses were thrust into the national spotlight earlier this year as the cause of death for Betsy Arakawa, the classical pianist and wife of late actor Gene Hackman.
The researchers' findings, published in PLOS Pathogens, show how Andes virus, the only hantavirus known to spread from person to person, infects a wide range of tissues. The researchers also identified promising compounds that blocked the virus in lab tests, offering hope for future treatments.
Hantaviruses have been a global health concern since the 1950s, when they caused thousands of cases of hemorrhagic fever during the Korean War. Today, they continue to cause sporadic outbreaks around the world, with mortality rates ranging from 1% to 40%, depending on the strain of the virus.
In the U.S., Sin Nombre virus has caused cases of severe respiratory illness, while Old World Hantaan virus is known for causing kidney disease in Asia. Scientists are particularly worried about Andes virus, found in South America, because it is the first hantavirus known to spread between people. Recent deaths in New Mexico and California have underscored the ongoing risk these viruses present.
"Hantaviruses pose a serious threat to public health, yet we know little about how they attack the human body," said Dr. Vaithi Arumugaswami, senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research 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."
Studying infection with organoids
Scientists rely on animal models — usually hamsters— to study how viral infections spread throughout whole organ systems. But the extreme infectiousness of hantaviruses, combined with the need for biosafety level 4 containment, makes it very difficult to study their systemic effects in animals. To overcome this, the UCLA-led team used human stem cells to grow organoids — 3D mini organs that mimic the structure and function of human tissues.
The team exposed these organoid models to three hantaviruses, Andes virus, Hantaan virus and Sin Nombre virus, to see how each infected the different organs. The differences were striking.
Andes virus infected all cell types tested — lung epithelial and endothelial cells, cardiomyocytes and astrocytes – while Hantaan virus infected heart and brain cells more 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," said Arunachalam Ramaiah, co-senior author of the new study. "It shows just how versatile — and dangerous — this virus can be."
The researchers also discovered that Andes virus disrupts cellular metabolism in alarming ways. In lung cells, the virus triggered inflammation and cell injury while shutting down cholesterol and fat-processing pathways. In heart organoids, the virus disrupted cell structure and stopped the heart cells from beating rhythmically.
"The virus reprograms cell metabolism to favor its own survival," said Arumugaswami, who is also 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 no currently approved treatments or widely available vaccines for hantaviruses. To address this gap, the researchers tested a panel of potential drugs on their human cell model system.
They found that urolithin B — a natural compound found in certain fruits and nuts — strongly inhibited Andes virus infection. The compound also restored normal metabolism in infected cells while leaving healthy cells largely unchanged. Another compound, the antiviral medication favipiravir, already approved in Japan to treat influenza, also blocked the virus.
"Two compounds, urolithin B and favipiravir, showed real promise in blocking Andes virus," said Nikhil Chakravarty, a co-author and medical student at California University of Science and Medicine. "It's early work, but it points us toward the possibility of new therapies where none currently exist."
Although hantavirus infections remain relatively rare in the U.S., warming temperatures and habitat shifts could increase risks as rodents seek shelter in more human-occupied areas.
"The impacts of climate change may bring people into more frequent contact with hantavirus carriers," said Arjit Vijey Jeyachandran, first author and a bioinformatics programmer at the David Geffen School of Medicine at UCLA. "That makes it even more important to understand how these viruses spread — and how we can stop them."
Additional authors include: 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.
This research was supported by the National Institutes of Health.
