Innovative Mini-Organ Models Unlock Insights into Hantavirus Treatment

Researchers from UCLA have developed miniature organ models derived from human stem cells, enabling a deeper understanding of hantaviruses, which are infrequently encountered but can be fatal. These viruses, primarily transmitted by rodents, have gained attention due to notable cases, including the recent death of a classical pianist.

Published in PLOS Pathogens, the study demonstrates how the Andes virus, the only hantavirus known for human-to-human transmission, infects various tissues. The investigation also revealed potential therapeutic compounds that effectively inhibited the virus in laboratory settings, raising hopes for future treatment options.

Hantaviruses have posed global health risks since the 1950s, leading to thousands of hemorrhagic fever cases during the Korean War. Today, these viruses sporadically cause outbreaks worldwide, with mortality rates varying between 1% and 40% based on the virus strain. In the United States, the Sin Nombre virus has resulted in severe respiratory issues, while the Hantaan virus is linked to kidney diseases in Asia. The Andes virus is particularly concerning due to its potential for person-to-person transmission, as highlighted by recent fatalities in New Mexico and California.

Dr. Vaithi Arumugaswami, a senior researcher involved in this study, emphasized the importance of understanding how hantaviruses infect the human body. By utilizing organoid systems, scientists can observe the behavior of these viruses in lung, heart, and brain tissues, paving the way for the identification of effective countermeasures.

Traditionally, animal models, especially hamsters, have been used to study viral infections. However, due to the extremely infectious nature of hantaviruses and the need for high-level containment, studying their systemic effects in animal subjects presents significant challenges. The UCLA team circumvented these issues by generating organoids that replicate human tissue structure and function.

The researchers exposed their organoid models to three different hantaviruses: the Andes virus, Hantaan virus, and Sin Nombre virus, revealing notable differences in infection patterns. The Andes virus was found to infect a wide range of cell types, including lung epithelial and endothelial cells, heart cells, and astrocytes, while the Hantaan virus showed a more selective infection profile, primarily targeting heart and brain cells, and the Sin Nombre virus predominantly affected lung endothelial cells.

This research provided the first evidence of the Andes virus's capacity to replicate efficiently within human lung organoids, indicating its versatility and potential danger. Furthermore, the Andes virus was shown to disturb cellular metabolism, leading to inflammation and cellular injury while hindering cholesterol and fat processing pathways. In heart organoids, the virus disrupted cell integrity and affected the rhythmic beating of heart cells.

Currently, there are no approved treatments or vaccines for hantavirus infections. To address this limitation, the researchers evaluated a selection of potential antiviral drugs using their human cell model system. Among the candidates, urolithin B--a natural compound found in certain fruits and nuts--demonstrated a strong ability to inhibit Andes virus infection, restoring normal metabolic functions in affected cells without harming healthy ones. Additionally, favipiravir, an antiviral medication previously approved in Japan for influenza, also showed efficacy against the virus.

While hantavirus infections remain relatively uncommon in the U.S., environmental changes may increase the likelihood of human contact with rodent carriers. The potential impacts of climate change could lead to more frequent encounters with these viruses, underscoring the urgency to comprehend their transmission dynamics and explore preventive measures.

This study included contributions from several authors, reinforcing the collaborative effort to tackle the challenges posed by hantaviruses and their associated health risks.