Neuro-Immune Responses of Astrocytes Following Alphavirus Infection

Viral infections of the central nervous system are a unique model to investigate neurodegenerative processes. One such virus is the alphavirus, Venezuelan equine encephalitis virus (VEE), a human pathogen. Using molecularly cloned virulent and attenuated VEE strains allows us to address the neuro-immune response to this virus-induced encephalitis in the well-defined murine model. Of particular importance are astrocytes, because of their central role in the homeostasis of neurons and their unique ability to modulate neuro-immune responses. The objective of this proposal is to characterize the role of astrocytes in the neuro-immune response following VEE infection in vivo. The central hypothesis is that VEE induces altered production of cytokines and neuronal growth factors in astrocytes that influence neuronal degeneration.

The Specific Aims of this research are to:

(1) investigate VEE infection in astrocytes in vivo;

(2) determine the mechanism of cell death following VEE infection of astrocytes; and

(3) establish the relationship of VEE infection and the production of cytokines and growth factors in astrocytes.

The rationale for the proposed research is that astrocytes form the supportive network of the central nervous system, that their activation is a hallmark of neurodegenerative processes, and that they are susceptible to VEE infection. With results from these experiments, we expect to contribute knowledge regarding neurodegenerative pathways and to the development of new approaches for prevention and management of these devastating diseases.

Final Report is available on NTRL at: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/ADA421190...