Inhibition of transient receptor potential vanilloid 1 (TRPV1) channel regulates chikungunya virus infection in macrophages
ARCHIVES OF VIROLOGY
Authors: Kumar, Sanjai P.; Nayak, Tapas K.; Mahish, Chandan; Sahoo, Subhransu S.; Radhakrishnan, Anukrishna; De, Saikat; Datey, Ankita; Sahu, Ram P.; Goswami, Chandan; Chattopadhyay, Soma; Chattopadhyay, Subhasis
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 -Ca2+-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-.B (p65) expression and nuclear localization. However, both activation and inhibition of TRPV1 were found to enhance the expression and nuclear localization of pNF-.B (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.
Rheumatic manifestations of chikungunya: emerging concepts and interventions
NATURE REVIEWS RHEUMATOLOGY
Authors: Suhrbier, Andreas
The largest epidemic ever recorded for chikungunya, a disease caused by infection with the chikungunya virus (CHIKV), began in Africa in 2004 and spread to > 100 countries on four continents. The epidemic caused > 10 million cases of often debilitating rheumatic disease, classically involving rapid onset of fever and polyarthralgia, often with polyarthritis. The clinical diagnosis of chikungunya is often complicated by infections with dengue or Zika virus. For many individuals with chikungunya, the disease is benign and self-limiting; however, some patients have a complex spectrum of atypical and severe manifestations. Many patients also experience a chronic phase of the disease, primarily involving arthralgia (which can be protracted (> 1 year)), and a number of sequelae are also recognized. CHIKV-induced arthropathy arises from infection of multiple cell types in the joint and the infiltration of mainly mononuclear cells. Innate responses (primarily involving type I interferon responses and natural killer cells) and cognate responses (primarily involving CD4 T helper 1 cells), alongside activation of macrophages and monocytes, mediate CHIKV-induced arthritic immunopathology. Ideally, improved anti-inflammatory treatments should not compromise antiviral immunity. New concepts in mosquito control are being field tested and a number of CHIKV vaccines are being developed.