iScience
·
2024
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IF 4.6
Shengze Zhang,Chuming Luo,Qiqi Chen,Nina Li,Xinzhong Liao,Jiani Wu,Haolu Zha,Ting Xie,Shaohui Bai,Weijian Tian,Lin Zhu,Xuan Zou,Shisong Fang,Caijun Sun,Ying Jiang,Jianhui Yuan,Yuelong Shu,Nan Wu,Huanle Luo
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial in flavivirus infections, modulating the host immune response through interactions with viral proteins. Despite its importance, the relationship between TRAF6 and Zika virus (ZIKV) remains poorly understood. Our prior proteomics analysis revealed reduced TRAF6 protein levels in ZIKV-infected human trophoblast cells compared to non-infected controls. Subsequent studies in cell models and murine tissues confirmed a significant reduction in both TRAF6 mRNA and protein levels post-ZIKV infection. Further investigations unveiled that ZIKV induces P62-mediated degradation of TRAF6, with NS1 identified as the primary contributor. Co-localization and interaction studies demonstrated that NS1 promotes the association of P62, a key autophagy mediator, with TRAF6. Notably, our findings revealed TRAF6 enhances ZIKV infection, NS1 ubiquitination, NS1 expression, and the production of inflammatory cytokines and chemokines. These insights highlight the intricate TRAF6-ZIKV relationship, offering potential for drug targeting NS1-TRAF6 interactions to manage ZIKV infections effectively.
研究领域:
病毒学
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免疫学
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分子生物学
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
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IF 5.2
Di Kang,Guorui Zhang,Zhonghui Zhang,Zhancheng Tian,Shandian Gao,Guangyuan Liu,Guiquan Guan,Jianxun Luo,Hong Yin,Junzheng Du
Bluetongue virus (BTV) infection effectively activates the innate immune response, followed by the expression of interferon (IFN) and multiple interferon-stimulated genes (ISGs). ISG15 is one of the most induced ISGs, and often plays a role in inhibiting virus replication. This study aims to explore the role and specific mechanisms of ovine ISG15 (oISG15) in BTV infection. We found that the transcription level of oISG15 was upregulated in a time-dependent and BTV multiplicity of infection-dependent manner. The overexpression of exogenous oISG15 enhances BTV replication, whereas the knockdown of endogenous oISG15 inhibits BTV replication. The viral protein in wild-type oISG15-overexpressed cells and ISGylation defective oISG15-overexpressed cells have no significant differences, which indicated that oISG15 promoted BTV replication in an ISGylation-independent manner. A co-immunoprecipitation assay showed that four viral BTV proteins—VP3, VP4, VP5, and NS1—interacted with oISG15. We also found that the VP4 and NS1 proteins associated with ubiquitin via co-immunoprecipitation, and that oISG15 overexpression improved the stability of both proteins. Further results showed that the degradation of NS1 was involved in lysine 63-linked polyubiquitin. This suggested that oISG15 may interfere with NS1 degradation via the autophagy pathway. This study provides new insights on the interaction between BTV and ISG15, and enriches our understanding of the regulation and biological function of ISG15 with virus replication.
研究领域:
病毒学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2026
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IF 9.5
Wang Xugang,Zhang Chenxi,Yang Chengjie,Guo Xiaotong,Hu Siyun,Qian Chaonan,Liao Bingrui,Ashraf Usama,Jin Weiwei,Yang Fei,Ouyang Hehao,Liu Yixin,Chen Huanchun,Huang Qiuying,Si Youhui,Zhu Bibo,Cao Shengbo,Ye Jing
Orthoflaviviruses are recognized as significant emerging mosquito-borne pathogens globally. Members of the Japanese encephalitis (JE) serogroup can be distinguished from other orthoflaviviruses by the presence of an additional non-structural protein (NS1’). However, the role of the NS1’ protein in the virus’s life cycle and transmission remains incompletely understood. This study demonstrates that the acquisition of the secretory NS1’ protein from JE serogroup viruses by mosquitoes from infected hosts significantly suppresses the antiviral effect of the RNA interference pathway, thereby facilitating viral infection in mosquitoes. Furthermore, immunization of mice with the NS1’ protein showed considerable efficacy in preventing the transmission of orthoflaviviruses from mice to mosquitoes. These findings indicate that targeting the NS1’ protein may represent a promising strategy for controlling the spread of JE serogroup viruses and other orthoflaviviruses between vertebrate hosts and mosquitoes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
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IF 8.786
Qin Sheng,Huang Xianzhang,Qu Shaogang
Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.
研究领域:
病毒学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
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