Immune Predictors of Mortality After Ribonucleic Acid Virus Infection

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  • Graham, Jessica B.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Swarts, Jessica L.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Menachery, Vineet D.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Gralinski, Lisa E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Plante, Kenneth S.
    • Affiliation: School of Medicine, Department of Genetics
  • Morrison, Clayton R.
    • Affiliation: School of Medicine, Department of Genetics
  • Voss, Katheen M.
    • Other Affiliation: University of Washington School of Medicine
  • Green, Richard
    • Other Affiliation: University of Washington School of Medicine
  • Choonoo, Gabrielle
    • Other Affiliation: Oregon Health & Science University
  • Jeng, Sophia
    • Other Affiliation: Oregon Health & Science University
  • Miller, Darla R.
    • Affiliation: School of Medicine, Department of Genetics
  • Mooney, Michael A.
    • Other Affiliation: Oregon Health & Science University
  • McWeeney, Shannon K.
    • Other Affiliation: Oregon Health & Science University
  • Ferris, Martin T.
    • Affiliation: School of Medicine, Department of Genetics
  • de Villena, Fernando Pardo-Manuel
    • Affiliation: School of Medicine, Department of Genetics
  • Gale Jr., Michael
    • Other Affiliation: University of Washington School of Medicine
  • Heise, Mark T.
    • Affiliation: School of Medicine, Department of Genetics
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Lund, Jennifer M.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
Abstract
  • Background Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines as well as the early identification of individuals with the highest risk that may require supportive treatment. Methods We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, severe acute respiratory syndrome-coronavirus, and West Nile virus. Results The CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality after infection and strains exhibiting no mortality. We then used comprehensive preinfection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection. Conclusions These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.
Date of publication
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  • Article
Rights statement
  • In Copyright
Journal title
  • The Journal of infectious diseases
Journal volume
  • 221
Journal issue
  • 6
Page start
  • 882
Page end
  • 889
Language
  • English
ISSN
  • 15376613

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