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Published on: November 22, 2011
Murine cytomegalovirus is present in both chronic active and latent states in persistently infected mice
S A Yuhasz1, V B Dissette, M L Cook
1Department of Microbiology and Immunology, University of California, Los Angeles, Medical School 90024-1747.
Abstract:
Cytomegalovirus induces serious disease in immunosuppressed individuals, often from an "activated" persistent infection. Whether the infection is chronically active or latent is unknown. Using murine cytomegalovirus (MCMV) in mice as a model system, we examined persistent infections in spleen, lung, and bone marrow of infected animals. At 28 days after infection, no virus could be recovered from any organs tested except salivary glands, and here, virus was cleared by 48 days. Virus could be retrieved at all times by cocultivation of spleen or lung with permissive cells. In addition, MCMV DNA was always present in spleen, lung, and bone marrow. After acute infection, RNA from the MCMV immediate early-1 (ie-1) gene was routinely found only in the lung. In spleen and bone marrow, only one sample from each organ examined at these times contained ie-1 RNA, and the RNA in these two samples was present at levels comparable to that found in acute infection. This suggests that the virus had reactivated. The ie-1 RNA found in the lung was present at a much lower RNA:DNA ratio than that found at early times. Taken together, these results indicate that persistent MCMV exists simultaneously in both chronic active and latent states.
Insights
Persistent cytomegalovirus (CMV) infections in mice can be both chronically active and latent. Murine CMV (MCMV) DNA and RNA indicate simultaneous active and latent states in spleen, lung, and bone marrow.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Cytomegalovirus (CMV) causes severe disease in immunosuppressed individuals.
- Persistent CMV infections can be either chronically active or latent, but the state is often unknown.
- Murine cytomegalovirus (MCMV) serves as a model to study persistent infections.
Purpose of the Study:
- To investigate the state of persistent MCMV infections in mice.
- To differentiate between chronic active and latent MCMV states in spleen, lung, and bone marrow.
Main Methods:
- Mice were infected with MCMV.
- Persistent infections were examined in spleen, lung, and bone marrow at various time points.
- Virus recovery via cocultivation, MCMV DNA presence, and MCMV immediate early-1 (ie-1) gene RNA expression were assessed.
Main Results:
- Virus was cleared from most organs by 48 days post-infection, except salivary glands.
- MCMV DNA was consistently detected in spleen, lung, and bone marrow.
- ie-1 RNA was detected in the lung, and sporadically in spleen and bone marrow, suggesting reactivation.
- Lower RNA:DNA ratios in the lung indicated a different state compared to acute infection.
Conclusions:
- Persistent MCMV infections exist in a simultaneous chronic active and latent state.
- The findings provide insights into the complex nature of CMV persistence.
- Understanding these states is crucial for managing CMV in immunosuppressed populations.
