RESUMO
The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.
Assuntos
Lyssavirus/genética , Lyssavirus/imunologia , Sequência de Aminoácidos , Animais , Sequência Conservada , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Lyssavirus/classificação , Lyssavirus/patogenicidade , Dados de Sequência Molecular , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Vírus da Raiva/patogenicidade , Fatores de Transcrição STAT/imunologia , Homologia de Sequência de Aminoácidos , Transdução de Sinais/imunologia , Especificidade da Espécie , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
Ergothioneine (ET) is a unique natural antioxidant which mammalia acquire exclusively from their food. Recently, we have discovered an ET transporter (ETT; gene symbol SLC22A4). The existence of a specific transporter suggests a beneficial role for ET; however, the precise physiological purpose of ET is still unclear. A conspicuous site of high extracellular ET accumulation is boar seminal plasma. Here, we have investigated whether ETT is responsible for specific accumulation of ET in the boar reproductive tract. The putative ETT from pig (ETTp) was cloned and validated by functional expression in 293 cells. The highest levels of ETTp mRNA were detected by real-time RT-PCR in seminal vesicles, eye, and kidney; much less was present in bulbourethral gland, testis, and prostate. By contrast, there was virtually no ETT mRNA in rat seminal vesicles. ET content in boar reproductive tissues, determined by LC-MS/MS, closely matched the ETT expression profile. Thus, strong and specific expression of ETTp in boar seminal vesicles explains high accumulation of ET in this gland and hence also in seminal plasma. Previous reports suggest that the glutathione (GSH) content of seminal plasma correlates directly with ET content; however, a comprehensive analysis across several species is not available. We have measured ET and GSH in seminal plasma from human, boar, bull, stallion, and rabbit by LC-MS/MS. GSH levels in seminal plasma do not correlate with ET levels. This suggests that the function of ET, at least in this extracellular context, does not depend on redox cycling with GSH.
