資料載入中.....
|
請使用永久網址來引用或連結此文件:
http://ir.meiho.edu.tw/ir/handle/987654321/3675
|
| 題名: | Adenosine Deaminase Acting on RNA 1 Associates with Orf |
| 作者: | Liao, Guan-Ru;Yeu-Yang Tseng;Tseng, Ching-Yu;Lin, Fong-Yuan;Yamada, Yumiko;Liu, Hao-Ping;Kuan, Chih-Ying |
| 關鍵詞: | ADAR1;E3;PKR;dsRNA;interferon;Orf virus;Poxviridae |
| 日期: | 2019-04-18 |
| 上傳時間: | 2019-04-26T05:04:52Z (UTC)
|
| 摘要: | ABSTRACT Orf virus (ORFV) infects sheep and goats and is also an important zoonotic
pathogen. The viral protein OV20.0 has been shown to suppress innate immunity by targeting
the double-stranded RNA (dsRNA)-activated protein kinase (PKR) by multiple
mechanisms. These mechanisms include a direct interaction with PKR and binding with
two PKR activators, dsRNA and the cellular PKR activator (PACT), which ultimately leads
to the inhibition of PKR activation. In the present study, we identified a novel association
between OV20.0 and adenosine deaminase acting on RNA 1 (ADAR1). OV20.0
bound directly to the dsRNA binding domains (RBDs) of ADAR1 in the absence of
dsRNA. Additionally, OV20.0 preferentially interacted with RBD1 of ADAR1, which was essential
for its dsRNA binding ability and for the homodimerization that is critical for intact
adenosine-to-inosine (A-to-I)-editing activity. Finally, the association with OV20.0
suppressed the A-to-I-editing ability of ADAR1, while ADAR1 played a proviral role during
ORFV infection by inhibiting PKR phosphorylation. These observations revealed a
new strategy used by OV20.0 to evade antiviral responses via PKR.
IMPORTANCE Viruses evolve specific strategies to counteract host innate immunity.
ORFV, an important zoonotic pathogen, encodes OV20.0 to suppress PKR activation
via multiple mechanisms, including interactions with PKR and two PKR activators. In
this study, we demonstrated that OV20.0 interacts with ADAR1, a cellular enzyme responsible
for converting adenosine (A) to inosine (I) in RNA. The RNA binding domains,
but not the catalytic domain, of ADAR1 are required for this interaction. The
OV20.0-ADAR1 association affects the functions of both proteins; OV20.0 suppressed
the A-to-I editing of ADAR1, while ADAR1 elevated OV20.0 expression. The proviral
role of ADAR1 is likely due to the inhibition of PKR phosphorylation. As RNA editing
by ADAR1 contributes to the stability of the genetic code and the structure of RNA,
these observations suggest that in addition to serving as a PKR inhibitor, OV20.0
might modulate ADAR1-dependent gene expression to combat antiviral responses
or achieve efficient viral infection. |
| 顯示於類別: | [美容系] 期刊論文
|
文件中的檔案:
| 檔案 |
描述 |
大小 | 格式 | 瀏覽次數 |
|---|
| 林峰源e01912-18.full.pdf | | 2601Kb | Adobe PDF | 1 | 檢視/開啟 |
|
在MUIR中所有的資料項目都受到原著作權保護.
|
