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Studies of latent cytomegalovirus infection: the macrophage as a virus-harboring cell
Abstract:
During chronic infection of mice with mouse cytomegalovirus (MCMV), the virus was isolated from various tissues by cocultivation with allogeneic mouse embryonic fibroblasts (MEF). Infectious virus was recovered from over 15% of the pancreases, salivary glands, kidneys, lacrimal glands, and spleens. When activated macrophages were obtained by intraperitoneal injection of peptone into mice infected 3 months earlier, they harbored MCMV. Macrophages or lymphocytes were infected with MCMV in vitro and injected into normal mice intravenously. The peritoneal cavities of these mice were then stimulated by peptone injection 3 months after the transfer, and peritoneal or splenic macrophages and lymphocytes were cocultured with allogeneic MEF. MCMV was recovered from the peritoneal and splenic macrophages and not from the lymphocytes.
Insights
Mouse cytomegalovirus (MCMV) persists in various mouse tissues during chronic infection. Activated macrophages, not lymphocytes, harbor and transmit MCMV, indicating their role in viral persistence.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Mouse cytomegalovirus (MCMV) establishes persistent infections in its host.
- Understanding the cellular reservoirs of MCMV is crucial for managing chronic infections.
Purpose of the Study:
- To investigate the tissues and cell types harboring MCMV during chronic infection in mice.
- To determine the role of macrophages and lymphocytes in MCMV persistence and transmission.
Main Methods:
- Mice were chronically infected with MCMV.
- Virus isolation was performed by cocultivation of various tissues and cells with allogeneic mouse embryonic fibroblasts (MEF).
- Adoptive transfer experiments involved infecting macrophages or lymphocytes in vitro and injecting them into naive mice, followed by immune stimulation and analysis.
Main Results:
- Infectious MCMV was recovered from multiple organs, including pancreas, salivary glands, kidneys, lacrimal glands, and spleen, in chronically infected mice.
- Activated peritoneal macrophages from infected mice harbored MCMV.
- Adoptive transfer of MCMV-infected macrophages into normal mice led to viral recovery from peritoneal and splenic macrophages, but not lymphocytes.
Conclusions:
- Macrophages serve as a significant cellular reservoir for MCMV during chronic infection.
- MCMV can be transmitted via infected macrophages, highlighting their role in viral dissemination and persistence.
- Lymphocytes do not appear to harbor or transmit MCMV in this model.