Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

Introduction: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V (D) J recombination, play a crucial role in B- and T-cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection ; volume:65 ; number:3 ; year:2021 ; pages:134-143 ; extent:10 ; Intervirology ; 65, Heft 3 (2021), 134-143 (gesamt 10)

Beteiligte, Orts- und Zeitangaben

• Urheber: Lee, Han-Kyul ; Seo, Sun-Min ; Kim, Jun-Young ; Kim, Han-Woong ; Jeong, Eui-Suk ; Choi, Yang-Kyu

Weitere Informationen

• DOI: 10.1159/000520463
• URN: urn:nbn:de:101:1-2022071400465649919382
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:30 MESZ