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Viremia and glial nodule encephalitis after experimental systemic cytomegalovirus infection
J Booss1, S R Winkler, B P Griffith
1Virology Laboratories, VA Medical Center, West Haven, Connecticut.
Abstract:
Despite the importance of cytomegalovirus (CMV) infection of the central nervous system in acquired immune deficiency syndrome, a well characterized laboratory model of glial nodule encephalitis after systemic CMV infection is not available. We now report that after intraperitoneal infection of young guinea pigs with CMV, infection of the brain was routinely found in the 2nd week. Recovery of virus from the brain was achieved at the time of viremia. Histopathologic changes in the brain followed the recovery of virus and continued beyond the point that virus was cleared from the brain. Microglial nodules, which were sometimes observed in association with intranuclear inclusion bearing cells, were the predominant feature. Other histopathology included perivascular infiltrates, vascular endothelial swelling, subependymal infiltrates, and sporadic focal leptomeningitis. In comparison to our previous studies after intracerebral inoculation, parenchymal changes dominated and leptomeningitis was found infrequently. The present studies suggest that focal central nervous system infection by CMV may be relatively common, though clinically silent, in the course of systemic infection. Relevant to acquired immune deficiency syndrome, the model should facilitate studies of the mechanism of brain infection, local central nervous system host defense, and mechanisms of injury to the brain.
Insights
A new guinea pig model shows cytomegalovirus (CMV) causes brain infections, leading to microglial nodules and other changes, even when clinically silent. This model aids research into CMV central nervous system disease, particularly in acquired immune deficiency syndrome.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Cytomegalovirus (CMV) central nervous system (CNS) infection is a significant concern in acquired immune deficiency syndrome (AIDS).
- A well-characterized animal model for CMV-induced glial nodule encephalitis following systemic infection was lacking.
- Understanding CMV's impact on the CNS is crucial for managing opportunistic infections in immunocompromised individuals.
Purpose of the Study:
- To establish and characterize a new guinea pig model of CMV encephalitis after systemic infection.
- To investigate the temporal relationship between viral replication, histopathological changes, and clinical presentation in the CNS.
- To provide a platform for studying CMV neuroinvasion, host defense mechanisms, and neuropathogenesis relevant to AIDS.
Main Methods:
- Young guinea pigs were intraperitoneally infected with CMV.
- Viral recovery from the brain was assessed during the period of viremia.
- Histopathological examination of brain tissue was performed to identify characteristic lesions.
- Comparison of findings with previous studies involving intracerebral inoculation.
Main Results:
- CMV brain infection was consistently detected by the second week post-infection.
- Viral recovery from the brain correlated with systemic viremia.
- Histopathological changes, including microglial nodules and perivascular infiltrates, followed viral clearance.
- Parenchymal changes predominated over leptomeningitis, differing from intracerebral inoculation models.
Conclusions:
- Systemic CMV infection in guinea pigs reliably induces CNS pathology, characterized by microglial nodules.
- The established model mimics aspects of CMV brain infection seen in AIDS patients.
- This model will be valuable for studying CMV neuroinflammation, host responses, and injury mechanisms in the CNS.