PMID- 30556910
OWN - NLM
STAT- MEDLINE
DCOM- 20200318
LR  - 20200318
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 149
IP  - 4
DP  - 2019 May
TI  - Japanese Encephalitis Virus-induced let-7a/b interacted with the NOTCH-TLR7 
      pathway in microglia and facilitated neuronal death via caspase activation.
PG  - 518-534
LID - 10.1111/jnc.14645 [doi]
AB  - MicroRNAs (miRNAs) released from the activated microglia upon neurotropic virus 
      infection may exacerbate the neuronal damage. Here, we identified let-7a and 
      let-7b (let-7a/b) as one of the essential miRNAs over-expressed upon Japanese 
      Encephalitis virus (JEV) infection and released in the culture supernatant of the 
      JEV-infected microglial cells through extracellular vesicles. The let-7a/b was 
      previously reported to modulate inflammation in microglial cells through 
      Toll-like receptor 7 (TLR7) pathways; although their role in accelerating JEV 
      pathogenesis remain unexplored. Therefore, we studied the role of let-7a/b in 
      modulating microglia-mediated inflammation during JEV infection and investigated 
      the effect of let-7a/b-containing exosomes on primary neurons. To this end, we 
      examined let-7a/b and NOTCH signaling pathway in TLR7 knockdown (KD) mice. We 
      observed that TLR7 KD or inhibition of let-7a/b suppressed the JEV-induced NOTCH 
      activation possibly via NF-kappaB dependent manner and subsequently, attenuated 
      JEV-induced TNFalpha production in microglial cells. Furthermore, exosomes secreted 
      from let-7a/b over-expressed microglia when transferred to uninfected mice brain 
      induced caspase activation. Exosomes secreted from virus-infected or let-7a/b 
      over-expressed microglia when co-incubated with mouse neuronal (Neuro2a) cells or 
      primary cortical neurons also facilitated caspase activation leading to neuronal 
      death. Thus, our results provide evidence for the multifaceted role of let-7a/b 
      miRNAs in JEV pathogenesis. Let-7a/b can interact with TLR7 and NOTCH signaling 
      pathway and enhance TNFalpha release from microglia. On the other hand, the exosomes 
      secreted by JEV-infected microglia can activate caspases in uninfected neuronal 
      cells which possibly contribute to bystander neuronal death. Cover Image for this 
      issue: doi: 10.1111/jnc.14506.
CI  - (c) 2018 International Society for Neurochemistry.
FAU - Mukherjee, Sriparna
AU  - Mukherjee S
AD  - National Brain Research Center, Manesar, India.
FAU - Akbar, Irshad
AU  - Akbar I
AD  - National Brain Research Center, Manesar, India.
FAU - Kumari, Bharti
AU  - Kumari B
AD  - Translational Health Science and Technology Institute, Faridabad, India.
FAU - Vrati, Sudhanshu
AU  - Vrati S
AD  - Translational Health Science and Technology Institute, Faridabad, India.
AD  - Regional Center for Biotechnology, Faridabad, India.
FAU - Basu, Anirban
AU  - Basu A
AUID- ORCID: 0000-0002-5200-2054
AD  - National Brain Research Center, Manesar, India.
FAU - Banerjee, Arup
AU  - Banerjee A
AUID- ORCID: 0000-0002-0600-1763
AD  - Translational Health Science and Technology Institute, Faridabad, India.
AD  - Regional Center for Biotechnology, Faridabad, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190131
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, Notch)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (mirnlet7 microRNA, mouse)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Caspases/metabolism
MH  - Cell Death/physiology
MH  - Cells, Cultured
MH  - Encephalitis Virus, Japanese
MH  - Encephalitis, Japanese/*metabolism/pathology
MH  - Exosomes/metabolism
MH  - Gene Knockdown Techniques
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Microglia/*metabolism/*virology
MH  - Neurons/*pathology
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction/physiology
MH  - Toll-Like Receptor 7/metabolism
OTO - NOTNLM
OT  - JEV
OT  - MicroRNA
OT  - exosome
OT  - neuroinflammation
EDAT- 2018/12/18 06:00
MHDA- 2020/03/19 06:00
CRDT- 2018/12/18 06:00
PHST- 2018/10/15 00:00 [received]
PHST- 2018/11/30 00:00 [revised]
PHST- 2018/12/06 00:00 [accepted]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2020/03/19 06:00 [medline]
PHST- 2018/12/18 06:00 [entrez]
AID - 10.1111/jnc.14645 [doi]
PST - ppublish
SO  - J Neurochem. 2019 May;149(4):518-534. doi: 10.1111/jnc.14645. Epub 2019 Jan 31.