Page 18 - IBRO_RNA School_Abstract Book

Host MicroRNA: An important modulator of antiviral
immunity in Japanese Encephalitis virus infection

Anirban Basu

National Brain Research Center, Manesar, Haryana, India

Ability to regulate gene expression at the post-transcriptional level has enabled

miRNA to play a significant role in various cellular physiological processes.
They play a crucial role in various flaviviral infections including Japanese encephalitis
virus (JEV) by regulating various aspects of innate and adaptive immune

responses. Microglial activation comprises one of the key events in JEV-induced
neuroinflammation and in this context; the involvement of several miRNAs has
been assessed. Mir-29b has been observed to positively regulate

neuroinflammation upon JEV infection by targeting tumor necrosis factor alpha-
nduced protein 3 (TNFAIP3), a negative regulator of nuclear factor-kappaB
signalling. Similar to mir-29b, JEV-induced miR-155 expression results in increased
neuroinflammatory response by suppressing Src homology 2-containing inositol
phosphatase 1 (SHIP1). In addition to microglia induced neuroinflammation, JEV
infection is also characterized by infection of neurons causing their death. JEV
evades neuronal innate immunity and defy type-I interferons (IFNs). Host miRNAs
play a vital role when our innate immunity is confronted by viral infection.

Upregulation of neuronal mir-301a upon JEV infection abrogates type-I IFNs by
targeting IRF1 and SOCS5, thus culminating into amplification of vi-ral
propagation. Suppression of mir-301a expression in infected cells restored IFN-β
expression to normal thus imparting anti-viral immunity. It has been
observed that JEV infection induces classical activation (M1) of microglia that drive
the production of pro-inflammatory cytokines, while suppressing alternative
activation (M2) that could serve to dampen the inflammatory response.
Furthermore, in vivo neutralization of miR-301a in mouse brain restores NKRF
expression, thereby reducing inflammatory response, microglial activation and
neuronal apoptosis. This study suggests that the JEV-induced expression of
miR-301a positively regulates inflammatory response by suppressing NKRF
production, which might be targeted to manage viral-induced neuro-inflammation.

However, the influences of these host miRNAs in JEV infection have
important implications to develop effective antiviral strategy.