Department of Veterinary Medicine and Institute of Preventive Veterinary Sciences, Zhejiang University College of Animal Sciences, Hangzhou, 310058, Zhejiang, China.
Hainan Institute, Zhejiang University, Sanya, 572025, Hainan, China.
Virol J. 2022 Mar 5;19(1):39. doi: 10.1186/s12985-022-01764-8.
Influenza A viruses (IAVs) are zoonotic, segmented negative-stranded RNA viruses. The rapid mutation of IAVs results in host immune response escape and antiviral drug and vaccine resistance. RUNX1 is a transcription factor that not only plays essential roles in hematopoiesis, but also functions as a regulator in inflammation. However, its role in the innate immunity to IAV infection has not been well studied.
To investigate the effects of RUNX1 on IAV infection and explore the mechanisms that RUNX1 uses during IAV infection. We infected the human alveolar epithelial cell line (A549) with influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) and examined RUNX1 expression by Western blot and qRT-PCR. We also knocked down or overexpressed RUNX1 in A549 cells, then evaluated viral replication by Western blot, qRT-PCR, and viral titration.
We found RUNX1 expression is induced by IAV H1N1 PR8 infection, but not by poly(I:C) treatment, in the human alveolar epithelial cell line A549. Knockdown of RUNX1 significantly inhibited IAV infection. Conversely, overexpression of RUNX1 efficiently promoted production of progeny viruses. Additionally, RUNX1 knockdown increased IFN-β and ISGs production while RUNX1 overexpression compromised IFN-β and ISGs production upon PR8 infection in A549 cells. We further showed that RUNX1 may attenuate the interferon signaling transduction by hampering the expression of IRF3 and STAT1 during IAV infection.
Taken together, we found RUNX1 attenuates type I interferon signaling to facilitate IAV infection in A549 cells.
甲型流感病毒（IAV）是一种人畜共患的、具有负链 RNA 基因组的节段性病毒。IAV 的快速突变导致宿主免疫逃逸以及抗病毒药物和疫苗耐药性。RUNX1 是一种转录因子，不仅在造血过程中发挥重要作用，而且在炎症中作为调节剂发挥作用。然而，其在 IAV 感染固有免疫中的作用尚未得到很好的研究。
为了研究 RUNX1 对 IAV 感染的影响，并探讨 RUNX1 在 IAV 感染过程中所使用的机制，我们用流感病毒 A/Puerto Rico/8/34（H1N1）（PR8）感染人肺泡上皮细胞系（A549），并用 Western blot 和 qRT-PCR 检测 RUNX1 的表达。我们还在 A549 细胞中敲低或过表达 RUNX1，然后通过 Western blot、qRT-PCR 和病毒滴定评估病毒复制。
我们发现，在人肺泡上皮细胞系 A549 中，IAV H1N1 PR8 感染可诱导 RUNX1 表达，但 Poly（I：C）处理则不能。RUNX1 的敲低显著抑制了 IAV 感染。相反，RUNX1 的过表达有效地促进了子代病毒的产生。此外，RUNX1 敲低增加了 IFN-β 和 ISGs 的产生，而过表达 RUNX1 则在 A549 细胞感染 PR8 时削弱了 IFN-β 和 ISGs 的产生。我们进一步表明，RUNX1 可能通过在 IAV 感染过程中抑制 IRF3 和 STAT1 的表达来减弱干扰素信号转导。
综上所述，我们发现 RUNX1 通过削弱 IAV 感染过程中的 I 型干扰素信号转导来促进 A549 细胞中的 IAV 感染。
