Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5
| Autor: | Sunit K. Singh, Meghana Rastogi, Nikhil Sharma, Kanhaiya Lal Kumawat, Anirban Basu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Swine viruses medicine.medical_treatment Suppressor of Cytokine Signaling Proteins Biology Virus Replication Suppressor of cytokine signalling Article Virus Cell Line Mice 03 medical and health sciences Downregulation and upregulation microRNA medicine Animals Humans SOCS5 Encephalitis Japanese 3' Untranslated Regions Encephalitis Virus Japanese Mice Inbred BALB C Gene knockdown Multidisciplinary Virology Cell biology MicroRNAs STAT1 Transcription Factor 030104 developmental biology Cytokine Viral replication Microglia |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep27685 |
| Popis: | Japanese encephalitis virus (JEV) is a plus strand RNA virus, which infects brain. MicroRNAs are regulatory non-coding RNAs which regulate the expression of various genes in cells. Viruses modulate the expression of various microRNAs to suppress anti-viral signaling and evade the immune response. SOCS (Suppressor of cytokine signalling) family of proteins are negative regulators of anti-viral Jak-STAT pathway. In this study, we demonstrated the regulatory role of SOCS5 in Jak-STAT signaling and its exploitation by JEV through a microRNA mediated mechanism. JEV infection in human brain microglial cells (CHME3) downregulated the expression of miR-432 and upregulated SOCS5 levels. SOCS5 was validated as a target of miR-432 by using 3′UTR clone of SOCS5 in luciferase vector along with miR-432 mimic. The overexpression of miR-432 prior to JEV infection enhanced the phosphorylation of STAT1 resulting into increased ISRE activity and cellular inflammatory response resulting into diminished viral replication. The knockdown of SOCS5 resulted into increased STAT1 phosphorylation and suppressed viral replication. JEV infection mediated downregulation of miR-432 leads to SOCS5 upregulation, which helps the virus to evade cellular anti-viral response. This study demonstrated that JEV utilizes this microRNA mediated strategy to manipulate cellular immune response promoting JEV pathogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|