Michael J Oglesbee, DVM, PhD
College of Veterinary Medicine
Infection, Fever, Spinal Cord Diseases, hemorrhage, Encephalomyelitis, Vesicular Stomatitis, Meningioma, Lymphopenia
Cellular heat shock proteins (HSPs) are known for their support of viral gene expression, and for influencing innate and adaptive immune responses, yet nothing is known about how virus-HSP interaction may influence viral virulence. Our laboratory uses the mouse model of measles virus (MeV) neuronal infection in brain to establish the in vivo significance of this virus-host interaction. Using transgenic mice that selectively overexpress the major inducible 70 kDa HSP (hsp70) in neurons, we have shown that hsp70-dependent stimulation of MeV transcription causes enhanced neurovirulence in an immune compromised host, yet supports viral clearance in an immune competent host. Clearance requires the viral transcriptional response to hsp70, and is attributed to both increased innate and adaptive antiviral immune responses. Ongoing efforts are designed to establish mechanisms by which hsp70 may modulate these protective immune responses, either directly as a consequence of extracellular hsp70 release from infected cells, or indirectly as a consequence of hsp70-dependent changes in viral gene expression and/or cytopathic effect.