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Severe encephalitis resulting from coinfections with HIV and JC virus
R Vazeux1, M Cumont, P M Girard
1Unité d'Oncologie Virale Institut Pasteur, Paris, France.
Abstract:
We observed 3 cases of progressive multifocal leukoencephalopathy (PML) among frozen CNS samples obtained at autopsy from 102 adult AIDS patients. In 2 patients, PML was associated with severe HIV encephalitis. In those 2 cases, the areas of extensive JC-induced demyelination were massively infiltrated by HIV infected macrophages/microglial cells with evidence for localized increase of HIV encephalitis in PML lesions. Using immunohistochemistry and in situ hybridization, we demonstrated that each virus infects, in a latent or productive fashion, different CNS cell populations. Therefore, the extension of HIV encephalitis could not be related to an intracellular transactivation of 1 virus by the other. However, the results are consistent with dissemination of viral infection by the recruitment of HIV-infected macrophages to damaged areas of the brain. This phenomenon might be generalized to other pathogens that are frequently associated with HIV CNS infection. Early detection and treatment of opportunistic CNS lesions could be important to prevent extension of HIV encephalitis.
Insights
Progressive multifocal leukoencephalopathy (PML) in AIDS patients was linked to HIV encephalitis. HIV-infected macrophages may spread the infection to damaged brain areas, worsening outcomes.
Area of Science:
- Neuroimmunology
- Viral Pathogenesis
- Neuropathology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic demyelinating disease affecting the central nervous system (CNS).
- Human immunodeficiency virus (HIV) infection, particularly in advanced stages like acquired immunodeficiency syndrome (AIDS), increases susceptibility to opportunistic infections, including PML.
- Understanding the interplay between HIV and opportunistic pathogens in the CNS is crucial for managing neurological complications in AIDS patients.
Observation:
- Three cases of PML were identified in autopsy CNS samples from 102 adult AIDS patients.
- In two of these cases, PML was co-occurring with severe HIV encephalitis.
- Extensive JC virus-induced demyelination in PML lesions showed massive infiltration by HIV-infected macrophages/microglial cells.
Findings:
- Immunohistochemistry and in situ hybridization revealed that HIV and JC virus infect distinct CNS cell populations, either latently or productively.
- The observed extension of HIV encephalitis within PML lesions was not attributed to intracellular transactivation between the viruses.
- Findings suggest viral dissemination occurs via the recruitment of HIV-infected macrophages to areas of brain damage.
Implications:
- The recruitment of HIV-infected macrophages to damaged CNS areas may be a general mechanism for the spread of opportunistic infections in HIV-associated CNS disease.
- Early detection and treatment of opportunistic CNS lesions, such as PML, could be vital in preventing the exacerbation of HIV encephalitis.
- This study highlights the complex interactions between viral pathogens in the CNS of immunocompromised individuals and informs potential therapeutic strategies.