Researchers from the Icahn School of Medicine at Mount Sinai have generated the first induced pluripotent stem cells (iPSCs) from bats, gaining valuable insights into the intimate relationship between bats and viruses. This research opens the door to studying how viruses like SARS-CoV-2, which causes COVID-19, survive, spread and evade the immune system through molecular adaptations in new hosts.
The results of the team, published on February 21 i cellalso shed light on the unique properties of bats that underlie their remarkable defenses against aging and cancer.
“Our study suggests that bats have evolved mechanisms to tolerate a large load of viral sequences, and may have a more entwined relationship with viruses than previously thought,” says senior author Thomas Zwaka, MD, PhD, Professor of Cell, Development and Regeneration. Biology at Icahn Mount Sinai. “This takes on new relevance due to the fact that many bat species have been shown to tolerate and survive viruses with high mortality rates in humans, including SARS-CoV, SARS-CoV-2, MERS -CoV, and Marburg. It could be a modification of the innate immune response of bats, making them an asymptomatic and tolerant virus host.”
Induced pluripotent stem cells are created by genetically and chemically reprogramming skin or blood cells into newborn cells, which have the potential to become any cell in the body.
Until now, there have been no reliable cellular models to study bat biology or their responses to viral infections, which has hindered a deeper understanding of their genomic adaptations. The Mount Sinai team is helping to fill that void by creating induced pluripotent stem cells from the wild giant horseshoe bat (Rhinolophus ferrumequinum), which is the most common asymptomatic carrier of coronaviruses, including viruses closely related to SARS-CoV-2.
“Comparing bat iPSCs with other mammals allowed us to see a unique stem cell biology that had never been observed before,” says author Adolfo García-Sastre, PhD, Irene and Dr. Arthur M. Fishberg Professor of Medicine and Director of Global Health and Emerging Pathogens Institute at Icahn Mount Sinai. “The most extraordinary result was the presence of large virus-laden insects in bat stem cells that represent major viral families, including coronaviruses, without affecting the cells’ ability to proliferate and grow. This may suggest a new paradigm regarding virus tolerance as well as its symbiotic relationship between bats and viruses.”
Researchers believe that the bat stem cell model they have created will provide an exceptional tool for the scientific community. The study’s first author, Marion Dejosez, PhD, Associate Professor of Cell, Developmental and Regenerative Biology at Icahn Mount Sinai, points out that “pluripotent stem cells have the unique ability to divide indefinitely in culture and turn into immune cells and tissues (such as lung or gut epithelium), making them amenable to gene editing and molecular studies.”
This research, in turn, could help answer important questions such as how bats tolerate viral infections and whether they genetically simulate strategies used by viruses to evade the immune system, paving the way for ones for virus production. An additional question the study helps to answer is whether viruses act as fully capable agents and editors of host biology in a way that makes them rich sources of evolutionary instructions.
“Future research into bat stem cells will have a direct impact on all aspects of our understanding of bat biology, including bats’ amazing flight adaptations and the ability to locate distant or invisible objects through echolocation, the location of objects indicated by sound , as well as their exact location. longevity and extraordinary immunity,” explains Dr. Zwaka, whose laboratory at Mount Sinai focuses on fundamental questions of stem cell biology.
However, the biggest scientific gains are expected to be in the bat virus. “Our study establishes a platform to further understand the unique role that bats play among mammals as a reservoir of viruses,” says Dr. García-Sastre. “And that knowledge could provide the field with broad new insights into disease and therapies as we prepare for future pandemics.”
This study was funded by the National Institutes of Health, the National Institute of General Medical Sciences, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Huffington Foundation, ie