Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Robert M. Cox, Josef D. Wolf, Nicole A. Lieberman, Carolin M. Lieber, Hae-Ji Kang, Zachary M. Sticher, Jeong-Joong Yoon, Meghan K. Andrews, Mugunthan Govindarajan, Rebecca E. Krueger, Elizabeth B. Sobolik, Michael G. Natchus, Andrew T. Gewirtz, Rik L. deSwart, Alexander A. Kolykhalov, Khan Hekmatyar, Kaori Sakamoto, Alexander L. Greninger and Richard K. Plemper ()
Additional contact information
Robert M. Cox: Georgia State University Institute for Biomedical Sciences
Josef D. Wolf: Georgia State University Institute for Biomedical Sciences
Nicole A. Lieberman: University of Washington
Carolin M. Lieber: Georgia State University Institute for Biomedical Sciences
Hae-Ji Kang: Georgia State University Institute for Biomedical Sciences
Zachary M. Sticher: Emory University
Jeong-Joong Yoon: Georgia State University Institute for Biomedical Sciences
Meghan K. Andrews: Emory University
Mugunthan Govindarajan: Emory University
Rebecca E. Krueger: Emory University
Elizabeth B. Sobolik: University of Washington
Michael G. Natchus: Emory University
Andrew T. Gewirtz: Georgia State University Institute for Biomedical Sciences
Rik L. deSwart: Erasmus MC
Alexander A. Kolykhalov: Emory University
Khan Hekmatyar: Georgia State University
Kaori Sakamoto: University of Georgia
Alexander L. Greninger: University of Washington
Richard K. Plemper: Georgia State University Institute for Biomedical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45418-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45418-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45418-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().