Unique immune profiles in collaborative cross mice linked to survival and viral clearance upon infection
Jessica B. Graham,
Jessica L. Swarts,
Sarah R. Leist,
Alexandra Schäfer,
Timothy A. Bell,
Pablo Hock,
Joe Farrington,
Ginger D. Shaw,
Martin T. Ferris,
Fernando Pardo-Manuel de Villena,
Ralph S. Baric,
Jennifer M. Lund
Affiliations
Jessica B. Graham
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Jessica L. Swarts
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Sarah R. Leist
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Alexandra Schäfer
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Timothy A. Bell
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Pablo Hock
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Joe Farrington
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ginger D. Shaw
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Martin T. Ferris
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Fernando Pardo-Manuel de Villena
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ralph S. Baric
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Jennifer M. Lund
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Corresponding author
Summary: 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.
