Mouse Adenovirus Type 1 Persistence Exacerbates Inflammation Induced by Allogeneic Bone Marrow Transplantation
Christine J Chang1, Luzmariel Medina Sanchez1, Aditya Vageesh1
1Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Journal of Virology
|January 19, 2022
Summary
Adenovirus persistence in mice did not lead to reactivation after bone marrow transplantation (BMT). However, persistent adenovirus infection exacerbated graft-versus-host disease-like inflammation following BMT.
Area of Science:
- Virology
- Immunology
- Transplantation Medicine
Background:
- Human adenovirus infections pose significant risks to bone marrow transplantation (BMT) recipients, often due to viral reactivation.
- The cellular reservoirs and long-term effects of adenovirus persistence on host responses are not fully understood.
Purpose of the Study:
- To characterize mouse adenovirus type 1 (MAV-1) persistence in its natural host.
- To test if MAV-1 persistence exacerbates complications following allogeneic BMT.
Main Methods:
- Mice were intranasally infected with MAV-1, and viral DNA and transcripts were monitored over time.
- Persistent MAV-1 infection was established, and mice underwent allogeneic BMT.
- Host responses, including mortality, weight loss, inflammation, and graft-versus-host disease (GVHD)-like pathology, were assessed post-BMT.
Main Results:
- MAV-1 DNA persisted in multiple organs (lung, mediastinal lymph nodes, liver) for at least 150 days postinfection without detectable ongoing replication.
- IFN-γ deficiency did not affect MAV-1 persistence.
- No MAV-1 reactivation was observed in persistently infected mice post-BMT.
- Persistent MAV-1 infection did not increase mortality, weight loss, or pulmonary inflammation but led to more pronounced liver T cell infiltration and pro-inflammatory cytokine expression, indicative of exacerbated GVHD-like responses.
Conclusions:
- MAV-1 establishes long-term persistence in multiple organs without evidence of active replication.
- Adenovirus persistence can alter host responses to unrelated challenges, such as BMT, by exacerbating GVHD-like inflammation even without viral reactivation.
