title: Major histocompatibility complex haplotype determines hsp70-dependent protection against measles virus neurovirulence.
abstract: In vitro studies show that hsp70 promotes gene expression for multiple viral families, although there are few reports on the in vivo significance of virus-hsp70 interaction. Previously we showed that hsp70-dependent stimulation of Edmonston measles virus (Ed MeV) transcription caused an increased cytopathic effect and mortality in transgenic hsp70-overexpressing C57BL/6 mice (H-2(b)). The response to MeV infection is influenced by the major histocompatibility complex haplotype; H-2(d) mice are resistant to brain infection due to robust antiviral immune responses, whereas H-2(b) mice are susceptible due to deficiencies in this response. We therefore tested the hypothesis that the outcome of MeV-hsp70 interaction may be dependent upon the host H-2 haplotype. The impact of selective neuronal hsp70 overexpression on Ed MeV brain infection was tested with congenic C57BL/10 H-2(d) neonatal mice. In this context, hsp70 overexpression conferred complete protection against virus-induced mortality, compared to >30% mortality in nontransgenic mice. Selective depletion of T-cell populations showed that transgenic mice exhibit a diminished reliance on T cells for protection. Brain transcript analysis indicated enhanced innate immune activation and signaling through Toll-like receptors 2 and 4 at early times postinfection for transgenic infected mice relative to those for nontransgenic infected mice. Collectively, results suggest that hsp70 can enhance innate antiviral immunity through Toll-like receptor signaling, supporting a protective role for physiological responses that enhance tissue levels of hsp70 (e.g., fever), and that the H-2 haplotype determines the effectiveness of this response.
authors.affiliation: Department of Veterinary Biosciences, Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carsillo
authors.forename: Mary
authors.initials: M
authors.lastname: Carsillo
authors.forename: Zachary
authors.initials: Z
authors.lastname: Traylor
authors.forename: Päivi
authors.initials: P
authors.lastname: Rajala-Schultz
authors.forename: Phillip
authors.initials: P
authors.lastname: Popovich
authors.forename: Stefan
authors.initials: S
authors.lastname: Niewiesk
authors.forename: Michael
authors.initials: M
authors.lastname: Oglesbee