کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6021934 1580655 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TLR7 is a key regulator of innate immunity against Japanese encephalitis virus infection
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
TLR7 is a key regulator of innate immunity against Japanese encephalitis virus infection
چکیده انگلیسی


- TLR7 signaling is important in initiating innate antiviral and proinflammatory response following JEV-infection.
- Systemic TLR7 response is essential for survival of mice post JEV-infection.
- JEV genomic RNA is detected by TLR7 in neurons.
- Imiquimod treatment confers protection to Japanese encephalitis infected mice.

Toll-like receptor 7 (TLR7) known to recognize guanidine-rich ssRNA has been shown to mount vital host defense mechanism against many viruses including flaviviruses. Signal transduction through TLR7 has been shown to produce type-1 interferon and proinflammatory mediators, thereby initiating essential innate immune response against ssRNA viruses in hosts. Systemic and brain specific TLR7 knock-down mice (TLR7KD) were generated using vivo-morpholinos. These mice were then subcutaneously challenged with lethal dose of JEV (GP78 strain) and were subsequently analyzed for survival. Significant difference in susceptibility to JEV between wild-type and systemic TLR7KD mice was observed whereas, no difference in susceptibility to JEV infection was seen in brain-specific TLR7KD mice. Significant decreases in IFN-α and antiviral proteins were also observed in both TLR7KD mice along with increased viral loads in their brain. Owing to increased viral load, increases in levels of various proinflammatory cyto/chemokines, increased microglial activation and infiltration of peripheral immune cells in brain of TLR7KD mice were also observed. Immunocytochemistry and RNA co-immunoprecipitation performed with JEV-infected N2a or HT22 cells indicated endosomal localization and confirmed interaction between JEV ssRNA with TLR7. Treatment of mice with imiquimod, a TLR7 agonist, prior to JEV infection resulted in their increased survival. Overall, our results suggest that the TLR7 response following JEV infection promotes type-1 interferon production and generation of antiviral state which might contribute to protective effect in systemic infection.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 69, September 2014, Pages 235-247
نویسندگان
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