Immune Predictors of Mortality after Ribonucleic Acid Virus Infection

Jessica B. Graham, Jessica L. Swarts, Vineet D. Menachery, Lisa E. Gralinski, Alexandra Schäfer, Kenneth S. Plante, Clayton R. Morrison, Kathleen M. Voss, Richard Green, Gabrielle Choonoo, Sophia Jeng, Darla R. Miller, Michael A. Mooney, Shannon K. McWeeney, Martin T. Ferris, Fernando Pardo Manuel De Villena, Michael Gale, Mark T. Heise, Ralph S. Baric, Jennifer M. Lund

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)882-889
Number of pages8
JournalJournal of Infectious Diseases
Issue number6
StatePublished - Mar 15 2020


  • Collaborative Cross
  • Immune correlates of mortality
  • RNA virus infection

ASJC Scopus subject areas

  • General Medicine


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