Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The central nervous dysfunctions of lethargy, fever and anorexia are manifestations of sepsis that seem to be mediated by increased cytokine production. Here we demonstrate that tumor necrosis factor (TNF)-alpha, an essential mediator of endotoxin-induced sepsis, prevents the proteasome-dependent degradation of RGS7, a regulator of G-protein signaling. The stabilization of RGS7 by TNF-alpha requires activation of the stress-activated protein kinase p38 and the presence of candidate mitogen-activated protein kinase phosphorylation sites. In vivo, RGS7 is rapidly upregulated in mouse brain after exposure to either endotoxin or TNF-alpha, a response that is nearly abrogated in mice lacking TNF receptor 1. Our findings indicate that TNF-mediated upregulation of RGS7 may contribute to sepsis-induced changes in central nervous function.
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PMID:Upregulation of RGS7 may contribute to tumor necrosis factor-induced changes in central nervous function. 1042 8

Characterization of cellular receptors for human, simian, and feline immunodeficiency viruses that are tropic for lymphocytes and macrophages have revealed a common theme of a sequential binding of viral envelope proteins with two coreceptors to mediate virus infection of target cells. In contrast to these dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine infectious anemia virus (EIAV), exclusively infect cells of the monocyte-macrophage lineage to cause progressive degenerative diseases without clinical immunodeficiency. EIAV causes a uniquely dynamic disease that is characterized by recurrent disease episodes including fever, diarrhea, lethargy, anemia, and thrombocytopenia. Although EIAV provides an important animal model for lentivirus disease resulting from macrophage infection, to date there has been no definition of the specific cellular receptor(s) used by the equine lentivirus to infect target cells. In the current study, we have identified and cloned a functional receptor for EIAV, designated equine lentivirus receptor-1 (ELR1), related to the family of TNF receptor (TNFR) proteins. ELR1 was shown to be expressed in various equine cells permissive for EIAV replication in vitro, including monocytes and macrophages. In contrast, EIAV-resistant human, murine, and simian cells were negative for ELR1 expression but became susceptible to virus infection when transduced with a recombinant murine retrovirus expressing the ELR1. Thus, these results identify a specific functional receptor for a macrophagetropic lentivirus and indicate that infection by EIAV may be mediated by a single receptor, in contrast to coreceptors used by the lymphotropic immunodeficiency lentiviruses.
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PMID:A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus. 1598 54