The humanized DRAGA mouse (HLA-A2. HLA-DR4. RAG1 KO. IL-2R g c KO. NOD) establishes inducible and transmissible models for influenza type A infections. Issue 9 (1st September 2020)

• Record Type: Journal Article
• Authors: Mendoza, Mirian; Gunasekera, Devi; Pratt, Kathleen P.; Qiu, Qi; Casares, Sofia; Brumeanu, Teodor-D.
• Is Part Of: Human vaccines & immunotherapeutics. Volume 16:Issue 9(2020)
• Page Start: 2222
• Page End: 2237
• Publication Date: 2020-09-01
• Subjects: Humanized mouse -- pro-coagulation Factor 8 mRNA -- natural IAV transmission -- CD103 lung-resident T cells -- IAV gender-based resilience; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2020.1713605
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: We have engineered a Human Immune System (HIS)-reconstituted mouse strain (DRAGA mouse: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD) in which the murine immune system has been replaced by a long-term, functional HIS via infusion of CD34 + hematopoietic stem cells (HSC) from cord blood. Herein, we report that the DRAGA mice can sustain inducible and transmissible H1N1 and H3N2 influenza A viral (IAV) infections. DRAGA female mice were significantly more resilient than the males to the H3N2/Aichi infection, but not to H3N2/Hong Kong, H3N2/Victoria, or H1N1/PR8 sub-lethal infections. Consistently associated with large pulmonary hemorrhagic areas, both human and murine Factor 8 mRNA transcripts were undetectable in the damaged lung tissues but not in livers of DRAGA mice advancing to severe H1N1/PR8 infection. Infected DRAGA mice mounted a neutralizing anti-viral antibody response and developed lung-resident CD103 T cells. These results indicate that the DRAGA mouse model for IAV infections can more closely approximate the human lung pathology and anti-viral immune responses compared to non-HIS mice. This mouse model may also allow further investigations into gender-based resilience to IAV infections, and may potentially be used to evaluate the efficacy of IAV vaccine regimens for humans.