The lipopeptide Pam3CSK4 inhibits Rift Valley fever virus infection and protects from encephalitis.

Autor: Griesman T; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia Pennsylvania, United States of America., McMillen CM; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.; Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, United States of America., Negatu SG; Department of Microbiology, University of Pennsylvania, Philadelphia Pennsylvania, Unites States of America., Hulahan JJ; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia Pennsylvania, United States of America., Whig K; High throughput screening core, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Dohnalová L; Department of Microbiology, University of Pennsylvania, Philadelphia Pennsylvania, Unites States of America., Dittmar M; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia Pennsylvania, United States of America., Thaiss CA; Department of Microbiology, University of Pennsylvania, Philadelphia Pennsylvania, Unites States of America., Jurado KA; Department of Microbiology, University of Pennsylvania, Philadelphia Pennsylvania, Unites States of America., Schultz DC; High throughput screening core, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Hartman AL; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.; Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, United States of America., Cherry S; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia Pennsylvania, United States of America.; High throughput screening core, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jun 27; Vol. 20 (6), pp. e1012343. Date of Electronic Publication: 2024 Jun 27 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012343
Abstrakt: Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Griesman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje