Chandipura virus dysregulates the expression of hsa-miR-21-5p to activate NF-κB in human microglial cells

Abstract

Background Chandipura virus (CHPV) is a negative single-stranded RNA virus of the Rhabdoviridae family. CHPV infection has been reported in Central and Western India. CHPV causes acute encephalitis with a case fatality rate of 70 % and mostly affects children below 15 years of age. CHPV infection in brain leads to neuronal apoptosis and activation of the microglial cells. The microRNAs (miRNAs) are small endogenous non-coding RNA that regulate the gene expression. Viral infections perturb the expression pattern of cellular miRNAs, which may in turn affect the expression pattern of downstream genes. This study aims to investigate hsa-miR-21-5p mediated regulation of PTEN, AKT, NF-ĸBp65, IL-6, TNF-α, and IL-1β, in human microglial cells during CHPV infection. Methods To understand the role of hsa-miR-21-5p in CHPV infection, the human microglial cells were infected with CHPV (MOI-0.1). Real-time PCR, western blotting, Luciferase assay, over-expression and knockdown techniques were used to understand the role of hsa-miR-21-5p in the regulation of PTEN, AKT and, NF-ĸBp65, IL-6, TNF-α, and IL-1β in this study. Results The hsa-miR-21-5p was found to be upregulated during CHPV infection in human microglial cells. This led to the downregulation of PTEN which promoted the phosphorylation of AKT and NF-ĸBp65. Over-expression of hsa-miR-21-5p led to the decreased expression of PTEN and promoted further phosphorylation of AKT and NF-ĸBp65 in human microglial cells. However, the inhibition of hsa-miR-21-5p using hsa-miR-21-5p inhibitor restored the expression. Conclusions This study supports the role of hsa-miR-21-5p in the regulation of pro-inflammatory genes in CHPV infected human microglial cells.

Possible role of CNS microRNAs in Human Mpox virus encephalitis—a mini-review

“…The study showed that the microRNA upregulation suppress PTEN expression and activate NF-ĸB through PI3K/AKT pathway. NF-ĸB activation induce pro-inflammatory responses and may participate in CHPV induced neuroinflammation (Pandey et al 2021).…”

In vitro and in vivo testing of the antiviral effect of favipiravir (T705) against the neurotropic Chandipura virus

“…1 It is a vector-borne virus in the family Rhabdoviridae that is transmitted by the sand fly species Phlebotomus sp., Sergentomyia sp., and the mosquito Aedes aegypti. 2 CHPV primarily replicates in neurons, which can lead to neuroinflammation and neuronal cell death. 2 In pediatric patients, the fatality rate of CHPV infection ranges from 44% to 75%.…”

“…2 CHPV primarily replicates in neurons, which can lead to neuroinflammation and neuronal cell death. 2 In pediatric patients, the fatality rate of CHPV infection ranges from 44% to 75%. 3 Severe CHPV infection is characterized by high-grade fever, vomiting, and convulsions that can lead to coma and death within 48 h of hospitalization.…”

Aplicaciones clínicas de miR-21: revisión de la literatura

“…Los miRNA pueden clasificarse como provirales (cuando favorecen la replicación viral y la infección) o antivirales, según las acciones que ejerzan en sus genes blanco una vez que el virus ha entrado en la célula huésped (53). Se ha identificado la sobreexpresión de miR-21 en infecciones por virus de la hepatitis B y C, papiloma, Epstein Barr, chandipura y dengue (54,55). En la infección por virus chandipura, que ocasiona una encefalitis aguda, la sobreexpresión de hsa-miR-21-5p condujo a la disminución de la expresión de PTEN posterior activación de la vía de señalización PI3K/AKT que promueve a su vez la activación de NF-ĸB y la respuesta proinflamatoria (55).…”