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Central nervous system infection in a murine retrovirus-induced immunodeficiency syndrome
1Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Abstract:
Astrocyte-enriched primary glial cultures (AGC) from C57BL/6 mice were found to be highly susceptible to infection with the replication competent components of LP-BM5, consisting of the ecotropic and mink cell focus-inducing (MCF) helper murine leukemia viruses (MuLVs). The presence in infected AGC of defective LP-BM5 MuLV genome, a critical component for induction of the disease referred to as murine AIDS, was confirmed by Southern blot hybridization using a probe reactive with the p12 gag sequence of the 4.9 kb defective genome. Electron microscopic studies demonstrated C-type retrovirus particles in both astrocytes and microglial cells. In vivo studies demonstrated that the ecotropic MuLVs and the defective genome could be detected within AGC obtained form either 14-day-old mice following intraperitoneal inoculation or 7-day-old mice following intracranial inoculation. These findings suggest that: (1) the central nervous system (CNS) infection is present at an early stage in murine AIDS, (2) both astrocytes and microglial cells are possible CNS targets in which helper MuLVs replicate, and (3) these cells can harbor the defective genome that is a critical component for disease induction.
Insights
Murine retroviruses infect central nervous system cells, including astrocytes and microglial cells, early in the development of murine AIDS (acquired immunodeficiency syndrome). These cells harbor the defective genome essential for disease induction.
Area of Science:
- Neuroimmunology
- Virology
- Retroviral Research
Background:
- Murine AIDS (MAIDS) is a retrovirus-induced immunodeficiency syndrome in mice.
- LP-BM5 murine leukemia viruses (MuLVs) are implicated in MAIDS pathogenesis.
- The central nervous system (CNS) role in MAIDS is not fully understood.
Purpose of the Study:
- To investigate the susceptibility of CNS cells to LP-BM5 MuLV infection.
- To determine if astrocytes and microglial cells are targets for MuLV replication in vivo.
- To assess the early presence of MuLV components within the CNS during MAIDS.
Main Methods:
- Primary astrocyte-enriched glial cultures (AGC) from C57BL/6 mice were infected with LP-BM5 MuLV components.
- Southern blot hybridization was used to detect the defective LP-BM5 MuLV genome.
- Electron microscopy visualized retroviral particles in CNS cells.
- In vivo studies involved intraperitoneal and intracranial inoculation of mice.
Main Results:
- Astrocyte-enriched glial cultures (AGC) were highly susceptible to LP-BM5 MuLV infection.
- Southern blot confirmed the presence of the defective LP-BM5 MuLV genome in infected AGC.
- Electron microscopy revealed C-type retrovirus particles in both astrocytes and microglial cells.
- In vivo, ecotropic MuLVs and the defective genome were detected in AGC from inoculated mice.
Conclusions:
- Central nervous system infection occurs early in murine AIDS.
- Astrocytes and microglial cells are potential CNS targets for helper MuLV replication.
- These CNS cells can harbor the defective genome crucial for murine AIDS induction.