School of Biological Sciences, National Institute of Science Education & Research, Bhubaneswar, HBNI, Jatni, Khurda, Odisha, 752050, India.
Infectious Disease Biology, Institute of Life Sciences, (Autonomous Institute of Department of Biotechnology, Government of India), Nalco Square, Bhubaneswar, Odisha, 751023, India.
Arch Virol. 2021 Jan;166(1):139-155. doi: 10.1007/s00705-020-04852-8. Epub 2020 Oct 30.
Chikungunya virus (CHIKV), a virus that induces pathogenic inflammatory host immune responses, is re-emerging worldwide, and there are currently no established antiviral control measures. Transient receptor potential vanilloid 1 (TRPV1), a non-selective Ca-permeable ion channel, has been found to regulate various host inflammatory responses including several viral infections. Immune responses to CHIKV infection in host macrophages have been reported recently. However, the possible involvement of TRPV1 during CHIKV infection in host macrophages has not been studied. Here, we investigated the possible role of TRPV1 in CHIKV infection of the macrophage cell line RAW 264.7. It was found that CHIKV infection upregulates TRPV1 expression in macrophages. To confirm this observation, the TRPV1-specific modulators 5'-iodoresiniferatoxin (5'-IRTX, a TRPV1 antagonist) and resiniferatoxin (RTX, a TRPV1 agonist) were used. Our results indicated that TRPV1 inhibition leads to a reduction in CHIKV infection, whereas TRPV1 activation significantly enhances CHIKV infection. Using a plaque assay and a time-of-addition assay, it was observed that functional modulation of TRPV1 affects the early stages of the viral lifecycle in RAW 264.7 cells. Moreover, CHIKV infection was found to induce of pNF-κB (p65) expression and nuclear localization. However, both activation and inhibition of TRPV1 were found to enhance the expression and nuclear localization of pNF-κB (p65) and production of pro-inflammatory TNF and IL-6 during CHIKV infection. In addition, it was demonstrated by Ca imaging that TRPV1 regulates Ca influx during CHIKV infection. Hence, the current findings highlight a potentially important regulatory role of TRPV1 during CHIKV infection in macrophages. This study might also have broad implications in the context of other viral infections as well.
基孔肯雅病毒（CHIKV）是一种诱导致病性炎症宿主免疫反应的病毒，正在全球范围内重新出现，目前尚无既定的抗病毒控制措施。瞬时受体电位香草酸 1 型（TRPV1）是一种非选择性的 Ca 通透性离子通道，已被发现调节各种宿主炎症反应，包括几种病毒感染。最近有报道称，宿主巨噬细胞对 CHIKV 感染的免疫反应。然而，TRPV1 在宿主巨噬细胞中 CHIKV 感染中的可能作用尚未研究。在这里，我们研究了 TRPV1 在 RAW 264.7 巨噬细胞系 CHIKV 感染中的可能作用。结果发现，CHIKV 感染上调了巨噬细胞中 TRPV1 的表达。为了证实这一观察结果，使用了 TRPV1 特异性调节剂 5'-碘树脂毒素（5'-IRTX，TRPV1 拮抗剂）和树脂毒素（RTX，TRPV1 激动剂）。结果表明，TRPV1 抑制导致 CHIKV 感染减少，而 TRPV1 激活则显著增强 CHIKV 感染。通过噬斑试验和时间添加试验观察到，TRPV1 的功能调节影响 RAW 264.7 细胞中病毒生命周期的早期阶段。此外，发现 CHIKV 感染诱导 pNF-κB（p65）表达和核定位。然而，TRPV1 的激活和抑制均发现增强了 CHIKV 感染期间 pNF-κB（p65）的表达和核定位以及促炎 TNF 和 IL-6 的产生。此外，通过 Ca 成像证明 TRPV1 在 CHIKV 感染期间调节 Ca 内流。因此，目前的研究结果强调了 TRPV1 在巨噬细胞中 CHIKV 感染过程中的潜在重要调节作用。本研究对于其他病毒感染也可能具有广泛的意义。
