dUTPase ویروس آرتریت-انسفالیت بزی به طور منفی مسیر سیگنال‌دهی اینترفرون را تنظیم می‌کند

نوع مقاله : مقاله کامل

نویسندگان

چکیده

پیشینه: داکسی یوراسیل تری‌فسفات نوکلئوتید (dUTP) پیروفسفاتاز (dUTPase, DU) یک آنزیم از ویروس آرتریت-انسفالیت بزی (CAEV) است که اتصال dUTP را در DNA به حداقل می‌رساند. ویروس آرتریت-انسفالیت بزی تا حدی با تکیه بر توانایی خود برای فرار از ایمنی ذاتی سبب ایجاد عفونت‌های مقاوم می‌شود. اینترفرون β (IFN-β) یک نشانگر مهم برای ارزیابی سیستم ایمنی ذاتی است، و دارای طیف وسیعی از فعالیت‌های ضدویروسی است. هدف: این مطالعه به منظور بررسی جزئیات پاسخ IFN-β به عفونت با CAEV انجام شد. روش کار: بیان IFN-β و تکثیر سندای ویروس (SeV) و ویروس وزیکولار استوماتیت (VSV) با استفاده از واکنش زنجیره‌ای پلیمراز کمی زمان واقعی (qPCR) تعیین شد. اثر DU بر مسیر سیگنال‌دهی اینترفرون با استفاده از سنجش گزارشگر لوسیفراز مورد بررسی قرار گرفت. نتایج: در مطالعه ما بیان IFN-β به طور معنی‌داری باعث مهار شد و تکثیر SeV و VSV در سلول‌های با بیان بالای CAEV-DU تقویت شد. DU عنصر پاسخ تحریک شده توسط اینترفرون (ISRE) و فعالیت پروموترهای IFN-β که توسط مسیر RIG-I/MDA5/MAVS/TBK1 القا شدند را تحت تاثیر قرار داد، در حالی که بر آن‌هایی که توسط فاکتور 3 تنظیم کننده اینترفرون القا شده بودند (IRF3-5D) اثر نداشت. نتیجه‌گیری: پروتئین DU با مهار فعالیت مولکول‌های انتقال دهنده سیگنال در بالادست IRF3، تولید IFN-β را مهار کرده و در نتیجه به CAEV کمک می‌کند تا از ایمنی ذاتی فرار کند. یافته‌های حاصل از این کار شواهدی را برای درک عفونت پایدار و التهاب سیستم چندگانه CAEV فراهم می‌کند.

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موضوعات


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