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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 14, 2012 |
| Title |
Hsp70 and a Novel Axis of Type 1 Interferon-Dependent Antiviral Immunity in the Measles Virus-Infected Brain |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN-β in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN-β transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
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| Overall design |
Hsp70 expression in mice enhances gene expression related to antiviral immune response against MeV neurovirulence. We performed microarrays on whole brain tissues in mice to obtain an unbiased picture of how hsp70 alters host innate responses to viral infection.
Hsp70-overexpressing transgenic (TG) and non-transgenic (NT) mice were infected with MeV intracranially, and total brain mRNA harvested at 5 and 10 days post infection (d.p.i.) was analyzed, sampling the hemisphere opposite the side of viral inoculation. Analysis includes 6 groups: infected TG at 5 d.p.i. (n=4), infected TG at 10 d.p.i. (n=5), infected NT at 5 d.p.i. (n=4), infected NT at 10 d.p.i. (n=5), uninfected TG at 5 d.p.i. (n=4), and uninfected NT at 5 d.p.i. (n=4).
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| Contributor(s) |
Oglesbee M, Zhang J, Yu L |
| Citation(s) |
23135720 |
| Submission date |
Nov 13, 2012 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Lianbo Yu |
| Organization name |
The Ohio State University
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| Department |
Center for Biostatistics
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| Lab |
320 Lincoln Tower
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| Street address |
1800 Cannon Drive
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| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43210 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (26)
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| GSM1036424 |
Infected TG 5 d.p.i., rep4 |
| GSM1036425 |
Infected TG 10 d.p.i., rep5 |
| GSM1036426 |
Infected TG 10 d.p.i., rep6 |
| GSM1036427 |
Infected TG 10 d.p.i., rep7 |
| GSM1036428 |
Infected TG 10 d.p.i., rep8 |
| GSM1036429 |
Infected TG 10 d.p.i., rep9 |
| GSM1036430 |
Infected NT 5 d.p.i., rep1 |
| GSM1036431 |
Infected NT 5 d.p.i., rep2 |
| GSM1036432 |
Infected NT 5 d.p.i., rep3 |
| GSM1036433 |
Infected NT 5 d.p.i., rep4 |
| GSM1036434 |
Infected NT 10 d.p.i., rep5 |
| GSM1036435 |
Infected NT 10 d.p.i., rep6 |
| GSM1036436 |
Infected NT 10 d.p.i., rep7 |
| GSM1036437 |
Infected NT 10 d.p.i., rep8 |
| GSM1036438 |
Infected NT 10 d.p.i., rep9 |
| GSM1036439 |
Uninfected TG at 5 d.p.i., rep1 |
| GSM1036440 |
Uninfected TG at 5 d.p.i., rep2 |
| GSM1036441 |
Uninfected TG at 5 d.p.i., rep3 |
| GSM1036442 |
Uninfected TG at 5 d.p.i., rep4 |
| GSM1036443 |
Uninfected NT at 5 d.p.i., rep1 |
| GSM1036444 |
Uninfected NT at 5 d.p.i., rep2 |
| GSM1036445 |
Uninfected NT at 5 d.p.i., rep3 |
| GSM1036446 |
Uninfected NT at 5 d.p.i., rep4 |
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| Relations |
| BioProject |
PRJNA179489 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42264_RAW.tar |
100.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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