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Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection
Estefanía Rodríguez1,2, Wing Hang Ip1,2, Viktoria Kolbe1,2
1Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.
Abstract:
Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
Insights
A new humanized mouse model reveals human adenovirus (HAdV) can establish persistent infections in the bone marrow. This breakthrough helps study severe HAdV infections in immunocompromised patients, like stem cell transplant recipients.
Area of Science:
- Virology
- Immunology
- Transplantation Science
Background:
- Severe human adenovirus (HAdV) infections pose a significant risk to immunocompromised individuals, especially following stem cell transplantation.
- The hypothesis of HAdV reactivation causing severe infections lacked in vivo validation due to the absence of a suitable animal model.
- Understanding HAdV persistence is crucial for managing infections in vulnerable populations.
Purpose of the Study:
- To establish and validate a humanized mouse model for studying acute and persistent human adenovirus (HAdV) infections.
- To investigate the in vivo characteristics of HAdV infection, including mortality, pathology, and viral gene expression.
- To explore the potential for HAdV cellular reservoirs in immunocompromised hosts.
Main Methods:
- Development of a humanized mouse model to mimic HAdV infection.
- Analysis of acute infection parameters: mortality, weight loss, and organ pathology.
- Assessment of persistent infection: immune response and viral gene expression patterns.
Main Results:
- The humanized mouse model successfully reproduced features of both acute and persistent HAdV infection.
- Acute infection was associated with high mortality, significant weight loss, liver damage, and widespread viral protein expression.
- Persistent infection was asymptomatic, induced HAdV-specific adaptive immunity, and showed viral gene expression restricted to the bone marrow.
Conclusions:
- Humanized mice provide a valuable platform for studying HAdV pathogenesis and persistence.
- The bone marrow serves as a potential cellular reservoir for persistent HAdV infections.
- These findings have significant implications for understanding and treating HAdV in immunocompromised patients.
