Genetic dissection of innate immunity to infection: the mouse cytomegalovirus model.

@article{Beutler2005GeneticDO,
  title={Genetic dissection of innate immunity to infection: the mouse cytomegalovirus model.},
  author={Bruce Beutler and Karine Crozat and James A. Koziol and Philippe T Georgel},
  journal={Current opinion in immunology},
  year={2005},
  volume={17 1},
  pages={
          36-43
        }
}
Resistance to infection is largely inherited rather than acquired, and is encoded by a definable set of host genes designated the 'resistome'. Logically speaking, piecemeal disruption of the resistome gives us the best chance to define it, and the most spectacular advances in understanding innate immunity have grown from spontaneous or induced germline mutations of the resistome. Mutations induced by random germline mutagenesis have now become so numerous that we are nearly in a position to… Expand
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References

SHOWING 1-10 OF 50 REFERENCES
Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily
TLDR
It is determined that MCMV susceptibility in BXD-8 is associated with the deletion of Klra8 (formerly Ly49h), a member of the killer cell lectin-like receptor family a (Klra, formerly Ly49; refs. 9–12), which encode inhibitory or activating NK cell receptors that interact with MHC class I molecules. Expand
Transgenic Expression of the Activating Natural Killer Receptor Ly49H Confers Resistance to Cytomegalovirus in Genetically Susceptible Mice
TLDR
It is demonstrated that Ly49H is necessary and sufficient to confer MCMV resistance, and allelism between Cmv1 and Ly49h is formally demonstrated, to study possible pleiotropic effect of CmV1. Expand
Multifactorial protective mechanisms to limit viral replication in the lung of mice during primary murine cytomegalovirus infection.
TLDR
It is found that IFN-gamma, IFN -gamma-R, IRF-1, iNOS, and perforin-deficient mice developed significantly higher titers of infectious MCMV in the lung, compared to those observed in their respective wild-type controls. Expand
Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection.
  • K. Tabeta, P. Georgel, +10 authors B. Beutler
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2004
TLDR
The phenotypic effect of the Tlr9(CpG1) allele points to a critical role for TLR9 in viral sensing and identifies a vulnerable amino acid within the ectodomain of three TLR proteins, essential for a ligand response. Expand
Increased susceptibility to cytomegalovirus infection in beige mutant mice.
TLDR
In bone marrow chimeras, recipients of bg/bg marrow were more susceptible to MCMV and had lower NK cell responses after virus inoculation than did recipients of marrow from bg/+ donors. Expand
Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente.
TLDR
Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. Expand
Pivotal Role of KARAP/DAP12 Adaptor Molecule in the Natural Killer Cell–mediated Resistance to Murine Cytomegalovirus Infection
TLDR
This is the first study that shows a crucial role for a particular activating signaling pathway, in this case the one induced through KARAP/DAP12, in the NK cell–mediated resistance to an infection. Expand
Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h
TLDR
This work presents the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset, as well as some redistributions of NK cell subsets defined by monoclonal antibody directed against Ly49A, C/I, D, and G2. Expand
Molecular and biological characterization of new strains of murine cytomegalovirus isolated from wild mice
TLDR
The isolation in this study of four genetically distinct strains of MCMV from a single wild mouse and several strains from other individual mice demonstrates that multiple infections withMCMV may be commonplace in wild mice. Expand
Analysis of the complete DNA sequence of murine cytomegalovirus
TLDR
The complete DNA sequence of the Smith strain of murine cytomegalovirus (MCMV) was determined from virion DNA by using a whole-genome shotgun approach, and significant similarity to the genome of the sequenced human cytome Galavirus (HCMV), strain AD169 is evident. Expand
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