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1.
J Virol ; 87(2): 998-1009, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23135720

RESUMO

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-2(d) congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. The 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 nontransgenic (NT) mice 5 days after infection identified type I interferon (IFN) signaling, macrophage activation, and antigen presentation as the main differences linked to survival. The pivotal role of type I IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type I 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 I IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN-ß 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-ß transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, our results support a novel axis of type I IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.


Assuntos
Encéfalo/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Interferon Tipo I/imunologia , Vírus do Sarampo/imunologia , Sarampo/imunologia , Transdução de Sinais , Animais , Encéfalo/patologia , Encéfalo/virologia , Modelos Animais de Doenças , Macrófagos/imunologia , Masculino , Sarampo/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptor de Interferon alfa e beta/deficiência , Análise de Sobrevida , Transcriptoma
2.
Biochem Genet ; 51(9-10): 686-97, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23695555

RESUMO

The northeastern bulrush, Scirpus ancistrochaetus, is a federally endangered wetland plant species found primarily in Pennsylvania, USA. Data on the population genetic structure of this species are needed by conservation managers to prioritize conservation efforts. In this study, we used two genetic marker systems to examine diversity and structure of this species in populations throughout Pennsylvania. The first simple and inexpensive approach utilized RAPD primers; our second, more detailed approach relied on DNA sequencing of single nucleotide polymorphisms. We found genetic variation using both RAPDs and sequencing and found some overlap in information between the two methods, including clusters of related populations and the identification of a genetically unique population. Future studies will seek to examine variation across the full geographic range of the species.


Assuntos
Cyperaceae/genética , DNA de Plantas/genética , Espécies em Perigo de Extinção , Variação Genética , Conservação dos Recursos Naturais , Cyperaceae/classificação , Marcadores Genéticos , Pennsylvania , Polimorfismo de Nucleotídeo Único , Técnica de Amplificação ao Acaso de DNA Polimórfico , Análise de Sequência de DNA
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