The article details research on why individual cells exhibit variable susceptibility to viral infection, even within a homogeneous cell type. The authors used a retrospective single-cell technique called Rewind to identify specific intrinsic cell states, such as the TIG1-high state, that make cells highly susceptible to SARS-CoV-2 and, separately, a distinct state susceptible to influenza A virus. This research establishes that a cell's transcriptional state prior to infection is a major determinant of whether it will be infected, showing that ACE2 expression alone is insufficient to predict SARS-CoV-2 susceptibility. Furthermore, they link the identified susceptible states to factors that regulate viral entry and note the heterogeneous expression of these states in human lung tissue, correlating with inflammatory disease and

References:

• Reffsin S, Miller J, Ayyanathan K, et al. Single-cell susceptibility to viral infection is driven by variable cell states[J]. Cell, 2025.