UCLA Scientists Develop Mini-Organs to Study Hantavirus Infections

Researchers at UCLA have engineered miniature organ models using human stem cells to investigate the mechanisms by which hantaviruses infect human tissues. This innovative approach comes in response to the recent heightened awareness of hantavirus infections, particularly following the death of classical pianist Betsy Arakawa, the widow of actor Gene Hackman, due to complications from the virus. The findings of this study, published in PLOS Pathogens, reveal critical insights into how the Andes virus, known for its potential to spread between humans, impacts various organs.

The research highlights the global significance of hantaviruses, which have been a public health concern since the 1950s. Historically, these viruses have been responsible for thousands of cases of hemorrhagic fever, especially noted during the Korean War. Today, the mortality rates for hantavirus infections can range dramatically from 1% to 40%, depending on the specific strain. In the United States, the Sin Nombre virus has led to severe respiratory illnesses, while the Hantaan virus is recognized for its association with kidney disease in parts of Asia. Notably, the Andes virus, discovered in South America, is now a focal point of concern due to its ability to transmit between individuals, as underscored by recent fatalities in New Mexico and California.

Insights from Mini-Organ Models

Dr. Vaithi Arumugaswami, the senior author of the study and a faculty member at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, stated, “Hantaviruses pose a serious threat to public health, yet we know little about how they attack the human body.” The team’s development of human organoid systems allows for unprecedented observation of viral behavior within lung, heart, and brain tissues.

Traditionally, animal models, primarily hamsters, have been used to study viral infections. However, the highly infectious nature of hantaviruses necessitates biosafety level 4 containment, complicating research efforts. By utilizing stem cells, the UCLA researchers successfully created three-dimensional organoids that replicate human tissue characteristics. They exposed these organoids to three hantaviruses: Andes, Hantaan, and Sin Nombre, revealing significant differences in infection patterns.

The Andes virus demonstrated a capacity to infect all tested cell types, including lung epithelial and endothelial cells, heart cells, and astrocytes. In contrast, Hantaan virus selectively infected heart and brain cells, while Sin Nombre virus predominantly targeted lung endothelial cells. “This is the first evidence that Andes virus can replicate efficiently in human lung organoids,” remarked Arunachalam Ramaiah, co-senior author of the study. The findings emphasize the versatility and potential danger posed by the Andes virus.

The researchers also observed alarming disruptions in cellular metabolism caused by the Andes virus. In lung organoids, the virus induced inflammation and cell injury while inhibiting cholesterol and fat-processing pathways. In heart organoids, it adversely affected cell structure and disrupted rhythmic contractions. Dr. Arumugaswami noted, “The virus reprograms cell metabolism to favor its own survival,” suggesting a link to the severe organ damage reported in infected patients.

Potential Treatments on the Horizon

Currently, there are no approved treatments or effective vaccines available for hantavirus infections. To address this gap, the research team evaluated a range of potential antiviral compounds using their organoid system. They identified urolithin B, a natural compound found in certain fruits and nuts, as a strong inhibitor of Andes virus infection. This compound not only blocked the virus but also restored normal metabolic functions in the affected cells, while leaving healthy cells relatively unharmed.

Another promising candidate, the antiviral medication favipiravir, which is already approved in Japan for influenza treatment, also demonstrated effectiveness against the Andes virus. “Two compounds, urolithin B and favipiravir, showed real promise in blocking Andes virus,” stated Nikhil Chakravarty, a co-author and medical student at California University of Science and Medicine. While these results are preliminary, they suggest potential new avenues for therapy where options are currently limited.

Despite hantavirus infections being relatively uncommon in the U.S., factors such as climate change may increase the risk of outbreaks. As changing temperatures and shifting habitats bring rodents closer to human populations, understanding the transmission dynamics of hantaviruses becomes increasingly urgent. Arjit Vijey Jeyachandran, the first author and a bioinformatics programmer at the David Geffen School of Medicine at UCLA, emphasized, “The impacts of climate change may bring people into more frequent contact with hantavirus carriers. That makes it even more important to understand how these viruses spread — and how we can stop them.”

This research received support from the National Institutes of Health, highlighting the collaborative effort to address this global health challenge. The study included contributions from a diverse team of researchers, further reinforcing the importance of interdisciplinary approaches in combating emerging infectious diseases.