Inhibition of transient receptor potential vanilloid 1 (TRPV1) channel regulates chikungunya virus infection in macropha
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ORIGINAL ARTICLE
Inhibition of transient receptor potential vanilloid 1 (TRPV1) channel regulates chikungunya virus infection in macrophages P. Sanjai Kumar1 · Tapas K. Nayak1,2 · Chandan Mahish1 · Subhransu S. Sahoo1 · Anukrishna Radhakrishnan1 · Saikat De2 · Ankita Datey2 · Ram P. Sahu1 · Chandan Goswami1 · Soma Chattopadhyay2 · Subhasis Chattopadhyay1 Received: 6 October 2019 / Accepted: 8 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract 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 C a2+-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 5ˊ-iodoresiniferatoxin (5ˊ-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 Ca2+ imaging that TRPV1 regulates Ca2+ 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.
Introduction Transient receptor potential (TRP) channels constitute a superfamily of ion channels that are non-selective, polymodal gated, and permeable to cations [1–4]. TRP channels can conduct an array of both monovalent and divalent cations, such as Na+, Mg2+, and C a2+ [5, 6]. Based on amino acid sequence similarity, the mammalian TRP superfamily Handling Editor: Patricia Aguilar. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00705-020-04852-8) contains supplementary material, which is available to authorized users. * Soma Chattopadhyay [email protected] * Subhasis Chattopadhyay [email protected]
is divided into six subfamilies: TRPC
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