Differential expression of NADPH oxidase-2 (Nox-2) and nuclear factor-erythroid 2-related factor 2 (Nrf2) transcripts in peripheral blood mononuclear cells isolated from dengue patients

Abstract

The role of oxidative stress in the pathogenesis of dengue infection is not completely known. A recent study reveals the involvement of oxidative stress responsive molecules in the generation of host immune responses to dengue virus in vitro. Objective of the present study was to analyse the changes in the expression of oxidant-antioxidant genes Nox-2 (NADPH oxidase) and Nrf2 (nuclear factor-erythroid 2-related factor 2) in patients with dengue during the early phase of infection compared to other febrile illness (OFI) cases and healthy controls using Real-time qPCR assay. The study enrolled 88 dengue patients, 31 OFI cases, and 63 healthy individuals as controls. Out of 88 dengue cases, 32 were classified as severe dengue cases (SD) and remaining 56 patients as non-severe dengue (NSD). Blood samples were collected firstly at the time of admission and a second sampling was done from the available individuals (38 dengue and 13 OFI cases) at the time of defervescence. Total RNA was extracted from the Peripheral blood mononuclear cells and the transcripts level of Nox-2 and Nrf2 were analysed by qPCR. On DOA, both Nox-2 and Nrf2 expression was found to be down regulated in dengue and OFI cases (P \ 0.05) compared to healthy controls. Interestingly at defervescence, the transcript levels were found to be significantly increased in dengue cases unlike OFI, where no such increment was evidenced. From DOA to DOD, the study observed a signficant increase in the levels of Nox-2 transcripts (P \ 0.05) both in SD and NSD cases. But a significant Nrf2 activation was not observed in SD cases as we found in NSD cases. Thus a steady and significant increase in Nox-2 transcript level in severe, non-severe and secondary dengue infected groups observed in the current study supports the earlier reports on the involvement of anti-oxidant response in dengue severity. However further studies on its protein levels and mechanistic action would decipher the exact role of these potential molecules in the disease virulence.

Prothymosin α accelerates dengue virus-induced thrombocytopenia

“… 63 In peripheral blood mononuclear cells from dengue patients, downregulation of Nrf2 mRNA has been observed. 64 It has been shown that Nrf2 negatively regulates PLT production through competing with NF-E2, an erythroid transcription factor. NF-E2 dominates over Nrf2 to enhance megakaryocytic maturation by promoting ROS accumulation.…”

SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

“…In addition, Nrf2 prevents the spread of the influenza virus infection (Ramezani et al 2018 ). Nrf2 is a major regulator during viral infections; some infections activate Nrf2, though other viral infections may provoke Nrf2 independent of the antioxidant pathway (Cherupanakkal et al 2017 ). Remarkably, Nrf2 is involved in the host immune response in patients with dengue infection (Cherupanakkal et al 2017 ).…”

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

“…[ 145 ] Nrf2 is a major regulator during viral infections; some infections activate Nrf2, though other viral infections may provoke Nrf2 independent of the antioxidant pathway. [ 146 ] Remarkably, Nrf2 is involved in the host immune response in patients with dengue infection. [ 146 ] According to comparison research involving 88 dengue patients and 31 patients with other febrile illnesses, dengue patients had higher levels of Nrf2 expression in their human peripheral mononuclear cells than those with other febrile illnesses.…”

“…[ 146 ] Remarkably, Nrf2 is involved in the host immune response in patients with dengue infection. [ 146 ] According to comparison research involving 88 dengue patients and 31 patients with other febrile illnesses, dengue patients had higher levels of Nrf2 expression in their human peripheral mononuclear cells than those with other febrile illnesses. [ 146 ] Therefore, Nrf2 may be implicated in the virulence and pathogenesis of viral infections.…”

“…[ 146 ] According to comparison research involving 88 dengue patients and 31 patients with other febrile illnesses, dengue patients had higher levels of Nrf2 expression in their human peripheral mononuclear cells than those with other febrile illnesses. [ 146 ] Therefore, Nrf2 may be implicated in the virulence and pathogenesis of viral infections. These findings proposed that Nrf2 plays a crucial role in viral infections to counteract the associated OS and exaggerated inflammatory reactions.…”