Unique immune profiles in collaborative cross mice linked to survival and viral clearance upon infection.

The response to infection is generally heterogeneous and diverse, with some individuals remaining asymptomatic while others present with severe disease or a diverse range of symptoms. Here, we address the role of host genetics on immune phenotypes and clinical outcomes following viral infection by studying genetically diverse mice from the Collaborative Cross (CC), allowing for use of a small animal model with controlled genetic diversity while maintaining genetic replicates. We demonstrate variation by deeply profiling a broad range of innate and adaptive immune cell phenotypes at steady-state in 63 genetically distinct CC mouse strains and link baseline immune signatures with virologic and clinical disease outcomes following infection of mice with herpes simplex virus 2 (HSV-2) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work serves as a resource for CC strain selection based on steady-state immune phenotypes or disease presentation upon viral infection, and further, points to possible pre-infection immune correlates of survival and early viral clearance upon infection.
Competing Interests: S.R.L. and R.S.B. are listed on a patent for the SARS-CoV-2 MA10 virus (US 11225508 B1, “Mouse-adapted SARS-CoV-2 viruses and methods of use thereof”). Funding for this study was provided by NIH grant U19 AI100625 (to R.S.B.), R01 AI157253 (to R.S.B.), P01 AI132130 (to M.T.F. and F.P.M.d.V.), and R21 AI152559 (to J.M.L.).
(© 2024 The Author(s).)