title: Network analysis reveals common host protein/s modulating pathogenesis of neurotropic viruses.
abstract: Network analysis through graph theory provides a quantitative approach to characterize specific proteins and their constituent assemblies that underlie host-pathogen interactions. In the present study, graph theory was used to analyze the interactome designed out of 50 differentially expressing proteins from proteomic analysis of Chandipura Virus (CHPV, Family: Rhabdoviridae) infected mouse brain tissue to identify the primary candidates for intervention. Using the measure of degree centrality, that quantifies the connectedness of a single protein within a milieu of several other interacting proteins, DJ-1 was selected for further molecular validation. To elucidate the generality of DJ-1's role in propagating infection its role was also monitored in another RNA virus, Japanese Encephalitis Virus (JEV, Family: Flaviviridae) infection. Concurrently, DJ-1 got over-expressed in response to reactive oxygen species (ROS) generation following viral infection which in the early phase of infection migrated to mitochondria to remove dysfunctional mitochondria through the process of mitophagy. DJ-1 was also observed to modulate the viral replication and interferon responses along with low-density lipoprotein (LDL) receptor expression in neurons. Collectively these evidences reveal a comprehensive role for DJ-1 in neurotropic virus infection in the brain.
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Sourish
authors: S
authors: Ghosh
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Sriparna
authors: S
authors: Mukherjee
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Nabonita
authors: N
authors: Sengupta
authors: Department of Biochemistry, University of Calcutta, Kolkata- 700019, India.
authors: Arunava
authors: A
authors: Roy
authors: Department of Biochemistry, University of Calcutta, Kolkata- 700019, India.
authors: Dhritiman
authors: D
authors: Dey
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Surajit
authors: S
authors: Chakraborty
authors: Department of Biochemistry, University of Calcutta, Kolkata- 700019, India.|Amity University Kolkata, Newtown, Kolkata-700135, India.
authors: Dhrubajyoti
authors: D
authors: Chattopadhyay
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Arpan
authors: A
authors: Banerjee
authors: National Brain Research Centre, Manesar, Haryana-122051, India.
authors: Anirban
authors: A
authors: Basu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000821:virology; D063306:Mitophagy; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1 / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018116:Vesiculovirus / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014779:Virus Replication / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D011973:Receptors, LDL; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1