New generation humanized mice for virus research: comparative aspects and future prospects

Area of Science:

• Virology and Immunology
• In vivo disease modeling
• Transplantation immunology

Background:

• Humanized mice (hu-Mice) are crucial for studying human-specific viruses and testing therapies.
• Previous hu-Mice lacked fully functional human immune systems, limiting their utility.
• Newer generations of hu-Mice now support multilineage human hematopoiesis and adaptive immune responses.

Purpose of the Study:

• To highlight the advancements in humanized mouse models for studying human-specific viral infections.
• To discuss the capabilities and limitations of current hu-Mice models.
• To explore the potential of hu-Mice in virology research and therapeutic development.

Main Methods:

• Utilizing two primary hu-Mice models: human hematopoietic stem cell (hu-HSC) and bone marrow, liver, and thymus (BLT) transplantation models.
• Infecting hu-Mice with human-specific viruses (e.g., HIV-1, Dengue, EBV, HCV) via various routes, including mucosal.
• Analyzing cellular and humoral immune responses, including T cell maturation and antibody production.

Main Results:

• New hu-Mice models support multilineage hematopoiesis and generate key immune cells (T cells, B cells, macrophages, dendritic cells).
• Models allow for the study of human-specific viral pathogenesis and immune responses in vivo.
• Efficient IgM production observed, but suboptimal IgG responses due to inefficient immunoglobulin class switching; BLT mice show HLA-restricted T cell responses.

Conclusions:

• Advanced hu-Mice models are powerful tools for studying human-specific viral infections and evaluating treatment strategies.
• Ongoing research focuses on enhancing immune responses and cell reconstitution for more robust human immune system simulation.
• These models hold significant promise for antivirals, gene therapy, viral evolution studies, and monoclonal antibody generation.