[en] Pneumonia virus of mice (PVM) infection is a reference animal model for human respiratory syncytial virus (hRSV), a leading cause of lower respiratory tract disease in children under 5 years of age and in the elderly. This longitudinal study employed necropsy to examine macroscopic lesions, histological slides to assess microscopic lesions, and qRT-PCR to measure lung viral load and cytokine expression in PVM-infected mice from three different genetic backgrounds, spanning from day 1 to day 6 post-infection. Our analysis reveals a strong correlation between viral load and microscopic lesions across the 129/Sv, BALB/c, and SJL/J mouse lines, indicating that PVM pathogenicity is partially driven by the virus itself. Additionally, a significant correlation between cytokine levels and lesion severity was observed in 129/Sv and BALB/c mice, suggesting an important role of cytokines in disease progression. This study emphasizes the interplay between viral load and cytokine-driven tissue damage, with genetic background significantly influencing disease outcomes.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Levy, Etienne ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Gilliaux, Gautier ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Sarlet, Michaël ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP)
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Van Laere, Anne-Sophie ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Language :
English
Title :
Host-Strain-Specific Responses to Pneumonia Virus of Mice Infection: A Study of Lesions, Viral Load, and Cytokine Expression.
Battles M.B. McLellan J.S. Respiratory syncytial virus entry and how to block it Nat. Rev. Microbiol. 2019 17 233 245 30723301 PMC7096974 10.1038/s41579-019-0149-x
Munro A.P.S. Martinón-Torres F. Drysdale S.B. Faust S.N. The disease burden of respiratory syncytial virus in Infants Curr. Opin. Infect. Dis. 2023 36 379 384 10.1097/QCO.0000000000000952
Jiang M.Y. Duan Y.P. Tong X.L. Huang Q.R. Jia M.M. Yang W.Z. Feng L.Z. Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: A systematic review and meta-analysis World J. Pediatr. WJP 2023 19 1030 1040 10.1007/s12519-023-00743-5 37531038
Li Y. Wang X. Blau D.M. Caballero M.T. Feikin D.R. Gill C.J. Madhi S.A. Omer S.B. Simões E.A.F. Campbell H. et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic analysis Lancet 2022 399 2047 2064 10.1016/S0140-6736(22)00478-0 35598608
Dyer K.D. Garcia-Crespo K.E. Glineur S. Domachowske J.B. Rosenberg H.F. The Pneumonia Virus of Mice (PVM) model of acute respiratory infection Viruses 2012 4 3494 3510 10.3390/v4123494 23342367
Krempl C.D. Lamirande E.W. Collins P.L. Complete Sequence of the RNA Genome of Pneumonia Virus of Mice (PVM) Virus Genes 2005 30 237 248 10.1007/s11262-004-5631-4
Nicklas W. Bleich A. Mähler M. Viral Infections of Laboratory Mice The Laboratory Mouse 2nd ed. Academic Press New York, NY, USA 2012
Vicencio A.G. Susceptibility to bronchiolitis in infants Curr. Opin. Pediatr. 2010 22 302 306 10.1097/MOP.0b013e32833797f9
Zeng R. Li C. Li N. Wei L. Cui Y. The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma Cytokine 2011 53 1 7 10.1016/j.cyto.2010.09.011
Gilliaux G. Desmecht D. Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection Viruses 2022 14 98 10.3390/v14010098
Djabirska I. Delaval L. Tromme A. Blomet J. Desmecht D. Van Laere A.S. Longitudinal quantitative assessment of TMEV-IDD-induced MS phenotypes in two inbred mouse strains using automated video tracking technology Exp. Neurol. 2024 379 114851 10.1016/j.expneurol.2024.114851
Anh D.B. Faisca P. Desmecht D.J. Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains Am. J. Physiol. Lung Cell. Mol. Physiol. 2006 291 L426 L435 10.1152/ajplung.00483.2005
Glineur S. Tran Anh D.B. Sarlet M. Michaux C. Desmecht D. Characterization of the resistance of SJL/J mice to pneumonia virus of mice, a model for infantile bronchiolitis due to a respiratory syncytial virus PLoS ONE 2017 7 e44581 10.1371/journal.pone.0044581 23077483
Mei J. Riedel N. Grittner U. Endres M. Banneke S. Emmrich J.V. Body temperature measurement in mice during acute illness: Implantable temperature transponder versus surface infrared thermometry Sci. Rep. 2018 8 3526 10.1038/s41598-018-22020-6
Rosenberg H.F. Domachowske J.B. Pneumonia Virus of Mice (PVM): Exploring Novel Therapeutic Options in a Severe Respiratory Disease Model National Institute of Allergy and Infectious Diseases, NIH Humana Press Totowa, NJ, USA 2010 353 359 10.1007/978-1-60761-512-5_35
Feldman D.B. Gupta B.N. Histopathologic changes in laboratory animals resulting from various methods of euthanasia Lab. Anim. Sci. 1976 26 Pt 1 218 221 1271740
Zanza C. Romenskaya T. Manetti A.C. Franceschi F. La Russa R. Bertozzi G. Maiese A. Savioli G. Volonnino G. Longhitano Y. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy Medicina 2022 58 144 10.3390/medicina58020144 35208467
Hu B. Huang S. Yin L. The cytokine storm and COVID-19 J. Med. Virol. 2021 93 250 256 10.1002/jmv.26232
Murdaca G. Paladin F. Tonacci A. Isola S. Allegra A. Gangemi S. The Potential Role of Cytokine Storm Pathway in the Clinical Course of Viral Respiratory Pandemic Biomedicines 2021 9 1688 10.3390/biomedicines9111688
Tisoncik J.R. Korth M.J. Simmons C.P. Farrar J. Martin T.R. Katze M.G. Into the eye of the cytokine storm Microbiol. Mol. Biol. Rev. MMBR 2012 76 16 32 10.1128/MMBR.05015-11
Fajgenbaum D.C. June C.H. Cytokine Storm N. Engl. J. Med. 2020 383 2255 2273 10.1056/NEJMra2026131
Hammoudeh S.M. Hammoudeh A.M. Bhamidimarri P.M. Al Safar H. Mahboub B. Künstner A. Busch H. Halwani R. Hamid Q. Rahmani M. et al. Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients Front. Immunol. 2021 12 595150 10.3389/fimmu.2021.595150
Crosse K.M. Monson E.A. Beard M.R. Helbig K.J. Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling J. Innate Immun. 2017 10 85 93 10.1159/000484258 29186718
García-Sastre A. Biron C.A. Type 1 interferons and the virus-host relationship: A lesson in détente Science 2006 312 879 882 10.1126/science.1125676
Parekh N.J. Winship D. Van Dis E. Stetson D.B. Regulation and Dynamics of IFN-β Expression Revealed with a Knockin Reporter Mouse J. Immunol. 2024 213 1858 1868 10.4049/jimmunol.2400227 39475224
Schoenborn J.R. Wilson C.B. Regulation of interferon-gamma during innate and adaptive immune responses Adv. Immunol. 2007 96 41 101
Bonville C.A. Percopo C.M. Dyer K.D. Gao J. Prussin C. Foster B. Rosenberg H.F. Domachowske J.B. Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo BMC Immunol. 2009 10 14 10.1186/1471-2172-10-14 19298652
Herrero C. Hu X. Li W.P. Samuels S. Sharif M.N. Kotenko S. Ivashkiv L.B. Reprogramming of IL-10 activity and signaling by IFN-gamma J. Immunol. 2003 171 5034 5041 10.4049/jimmunol.171.10.5034
Glineur S.F. Bowen A.B. Percopo C.M. Garcia-Crespo K.E. Dyer K.D. Ochkur S.I. Lee N.A. Lee J.J. Domachowske J.B. Rosenberg H.F. Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFNγ) gene-deleted mice Virology 2014 468–470 140 149 10.1016/j.virol.2014.07.039
Percopo C.M. Ma M. Brenner T.A. Krumholz J.O. Break T.J. Laky K. Rosenberg H.F. Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection J. Immunol. 2019 202 871 882 10.4049/jimmunol.1800927
Roy M. Richard J.F. Dumas A. Vallières L. CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis J. Neuroinflamm. 2012 9 18 10.1186/1742-2094-9-18
Kaiser K. Prystaz K. Vikman A. Haffner-Luntzer M. Bergdolt S. Strauss G. Waetzig G.H. Rose-John S. Ignatius A. Pharmacological inhibition of IL-6 trans-signaling improves compromised fracture healing after severe trauma Naunyn-Schmiedeberg’s Arch. Pharmacol. 2018 391 523 536 10.1007/s00210-018-1483-7
Hou S.M. Chen P.C. Lin C.M. Fang M.L. Chi M.C. Liu J.F. CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway Arthritis Res. Ther. 2020 22 251 10.1186/s13075-020-02331-8 33087182
Korbecki J. Gąssowska-Dobrowolska M. Wójcik J. Szatkowska I. Barczak K. Chlubek M. Baranowska-Bosiacka I. The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Muscle and the Nervous System Int. J. Mol. Sci. 2022 23 4205 10.3390/ijms23084205 35457023
