School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 514400, China.
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China.
Int J Mol Sci. 2021 Apr 28;22(9):4668. doi: 10.3390/ijms22094668.
Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that , as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-β production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.
深入了解病毒-宿主相互作用是开发有效抗病毒策略的前提。传统上，抗原加工相关转运蛋白 1（TAP1）对于抗原呈递以调节适应性免疫至关重要。然而，其通过调节先天免疫信号来控制病毒感染的作用尚不完全清楚。在本研究中，我们报道，作为干扰素刺激基因（ISGs）的产物，对多种病毒（如单纯疱疹病毒 1（HSV-1）、腺病毒（AdV）、水疱性口炎病毒（VSV）、登革热病毒（DENV）、寨卡病毒（ZIKV）和流感病毒（PR8）等）具有广泛的抗病毒活性。通过一系列功能丧失和功能获得实验进一步证实了 TAP1 的这种抗病毒活性。我们的进一步研究表明，TAP1 通过激活 TANK 结合激酶 1（TBK1）和干扰素调节因子 3（IRF3）信号转导，显著促进干扰素（IFN）-β的产生。我们的工作强调了 TAP1 通过调节先天免疫发挥广泛的抗病毒功能，这与其抗原呈递的已知功能无关。本研究将为开发针对新发传染病的新型疫苗接种和免疫治疗策略提供思路。
