Bat pluripotent stem cells reveal unusual entanglement between host and viruses.

Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However, there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) and the greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences, particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.
Competing Interests: Declaration of interests T.P.Z., M.D., and A.G.S. are inventors on patents and patent applications on the use of bat iPS cells, owned by the Icahn School of Medicine at Mount Sinai, New York. T.P.Z. and R.A.Y. are founders and shareholders of Paratus Sciences, and R.A.Y. is a founder and shareholder of Syros Pharmaceuticals, Camp4 Therapeutics, Omega Therapeutics, and Dewpoint Therapeutics. The A.G.S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-Fold LLC, Model Medicines, and Merck, outside of the reported work. A.G.S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, and Pfizer, outside of the reported work. A.G.S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. A.M. is the creator of Omics Bioinformatics and owns all the stocks of this company. R.P.S. has a consulting agreement with Sema4 involving cash and is also a stockholder of this company. A.P. and S.D.W.F. are employees of Microsoft Corporation. S.D.W.F. is co-founder of DIOSynVax, Ltd. and an inventor on patent applications on the design of vaccine immunogens for the prevention of virus infections, outside of the reported work.
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