A Two-Dimensional Human Minilung System (Model) for Respiratory Syncytial Virus Infections

Human respiratory syncytial virus (HRSV) is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs). The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV-host interactions.This work has been supported by grants MPY-1038/14 and MPY-1146/16 from ISCIII to A.Z., grant PI15CIII/00024 from ISCIII to I.M., grants MPY-1412/09 and PI-10/00291 (MICINN-ISCIII), SAF2015-71140-R (MINECO) and S2010/BMD-2336 (NEUROSTEMCM consortium from Community of Madrid) to ILS