Selected Grantee Publications
- Clear All
- 2 results found
- Rodent Models
- niddk
- HIV/AIDS
A Germ-Free Humanized Mouse Model Shows the Contribution of Resident Microbiota to Human-Specific Pathogen Infection
Wahl et al., Nature Biotechnology. 2023.
https://www.nature.com/articles/s41587-023-01906-5
Germ-free (GF) mice are of limited value in the study of human-specific pathogens because they do not support their replication. In this report, investigators developed a GF humanized mouse model using the bone marrow–liver–thymus platform to provide a robust and flexible in vivo model that can be used to study the role of resident microbiota in human health and disease. They demonstrated that resident microbiota promote viral acquisition and pathogenesis by using two human-specific pathogens, Epstein–Barr virus and HIV. Supported by ORIP (P40OD010995), FIC, NIAID, NCI, and NIDDK.
Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection
Abeynaike et al., Viruses. 2023.
https://www.mdpi.com/1999-4915/15/2/365
A major obstacle to human natural killer (NK) cell reconstitution is the lack of human interleukin‑15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor. Researchers show that immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice expressing a transgene encoding human IL-15 (NSG-Tg(IL-15)) have physiological levels of human IL-15 and support long-term engraftment of human NK cells when transplanted with human umbilical cord blood–derived hematopoietic stem cells (HSCs). These mice demonstrate robust and long-term reconstitution with human immune cells but do not develop graft-versus-host disease, allowing long-term studies of human NK cells. The HSC-engrafted mice can sustain HIV-1 infection, resulting in human NK cell responses. This work provides a robust novel model to study NK cell responses to HIV-1. Supported by ORIP (R24OD026440), NIAID, NCI, and NIDDK.