Immune Predictors of Mortality After Ribonucleic Acid Virus Infection

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Oct 18

PMID 31621854

Citations 8

Authors

Jessica B Graham

Jessica L Swarts

Vineet D Menachery

Lisa E Gralinski

Alexandra Schafer

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19.

Baker C, Duso D, Kothapalli N, Hart T, Casey S, Cookenham T Sci Rep. 2024; 14(1):25147.

PMID: 39448712 PMC: 11502910. DOI: 10.1038/s41598-024-77087-1.

Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19.

Baker C, Duso D, Kothapalli N, Hart T, Casey S, Cookenham T Res Sq. 2024; .

PMID: 39149485 PMC: 11326417. DOI: 10.21203/rs.3.rs-4675061/v1.

Neuroinvasive Flavivirus Pathogenesis Is Restricted by Host Genetic Factors in Collaborative Cross Mice, Independently of .

Jasperse B, Mattocks M, Noll K, Ferris M, Heise M, Lazear H J Virol. 2023; 97(7):e0071523.

PMID: 37310228 PMC: 10373552. DOI: 10.1128/jvi.00715-23.

Forward genetic screen of homeostatic antibody levels in the Collaborative Cross identifies MBD1 as a novel regulator of B cell homeostasis.

Hampton B, Plante K, Whitmore A, Linnertz C, Madden E, Noll K PLoS Genet. 2022; 18(12):e1010548.

PMID: 36574452 PMC: 9829176. DOI: 10.1371/journal.pgen.1010548.

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Schafer A, Leist S, Gralinski L, Martinez D, Winkler E, Okuda K mBio. 2022; 13(4):e0145422.

PMID: 35862771 PMC: 9426612. DOI: 10.1128/mbio.01454-22.

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