Interferon-Inducible Protein IFI35 Negatively Regulates RIG-I Antiviral Signaling and Supports Vesicular Stomatitis Virus Replication

水泡性口炎病毒 生物 钻机-I 干扰素 病毒复制 小干扰RNA 先天免疫系统 病毒学 细胞生物学 报告基因 病毒 基因 基因表达 免疫系统 核糖核酸 遗传学
作者
Anshuman Das,Phat X. Dinh,Debasis Panda,Asit K. Pattnaik
出处
期刊:Journal of Virology [American Society for Microbiology]
卷期号:88 (6): 3103-3113 被引量:92
标识
DOI:10.1128/jvi.03202-13
摘要

In a genome-wide small interfering RNA (siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) as a factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I·C)-induced inhibition of VSV replication. Promoter-driven reporter gene assays demonstrated that IFI35 overexpression suppressed the activation of IFN-β and ISG56 promoters, whereas its depletion had the opposite effect. Further investigation revealed that IFI35 specifically interacted with retinoic acid-inducible gene I (RIG-I) and negatively regulated its activation through mechanisms that included (i) suppression of dephosphorylation (activation) of RIG-I and (ii) proteasome-mediated degradation of RIG-I via K48-linked ubiquitination. Overall, the results presented here suggest a novel role for IFI35 in negative regulation of RIG-I-mediated antiviral signaling, which will have implications for diseases associated with excessive immune signaling.Mammalian cells employ a variety of mechanisms, including production of interferons (IFNs), to counteract invading pathogens. In this study, we identified a novel role for a cellular protein, IFN-inducible protein 35 (IFP35/IFI35), in negatively regulating the host IFN response during vesicular stomatitis virus (VSV) infection. Specifically, we found that IFI35 inhibited activation of the RNA sensor, the retinoic acid-inducible gene I (RIG-I), leading to inhibition of IFN production and thus resulting in better replication of VSV. The identification of a cellular factor that attenuates the IFN response will have implications toward understanding inflammatory diseases in humans that have been found to be associated with defects in the regulation of host IFN production, such as systemic lupus erythematosus and psoriasis.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
晴空发布了新的文献求助10
刚刚
Tatw完成签到 ,获得积分10
2秒前
4秒前
4秒前
赘婿应助独特书芹采纳,获得10
5秒前
xinmindeng发布了新的文献求助10
5秒前
领导范儿应助苏源智采纳,获得10
9秒前
咖咖咖喱发布了新的文献求助10
9秒前
饼藏发布了新的文献求助80
9秒前
呓语完成签到,获得积分10
13秒前
15秒前
Yyy完成签到 ,获得积分10
20秒前
朝昭照完成签到,获得积分10
20秒前
21秒前
24秒前
朝昭照发布了新的文献求助10
24秒前
24秒前
天啦噜完成签到 ,获得积分10
24秒前
圆圆小悦完成签到,获得积分10
25秒前
minmin959完成签到,获得积分10
26秒前
26秒前
无畏阿玲发布了新的文献求助10
27秒前
29秒前
xzz发布了新的文献求助10
29秒前
圆圆小悦发布了新的文献求助10
31秒前
斯文败类应助痴情的绮菱采纳,获得10
32秒前
66完成签到,获得积分10
32秒前
顾矜应助你好采纳,获得30
33秒前
唐同学发布了新的文献求助10
35秒前
受伤松鼠完成签到 ,获得积分10
36秒前
驿寄梅花发布了新的文献求助10
37秒前
tony发布了新的文献求助10
38秒前
xzz完成签到,获得积分10
39秒前
fly发布了新的文献求助10
40秒前
41秒前
Jasper应助梦幻采纳,获得10
42秒前
42秒前
糟糕的道罡完成签到,获得积分10
42秒前
英俊的铭应助驿寄梅花采纳,获得10
44秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Very-high-order BVD Schemes Using β-variable THINC Method 830
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3248513
求助须知:如何正确求助?哪些是违规求助? 2891915
关于积分的说明 8269223
捐赠科研通 2559929
什么是DOI,文献DOI怎么找? 1388807
科研通“疑难数据库(出版商)”最低求助积分说明 650897
邀请新用户注册赠送积分活动 627798