Chandipura virus perturbs cholesterol homeostasis leading to neuronal apoptosis

Ghosh, Sourish ; Mukherjee, Sriparna ; Basu, Anirban (2015) Chandipura virus perturbs cholesterol homeostasis leading to neuronal apoptosis Journal of Neurochemistry, 135 (2). pp. 368-380. ISSN 0169-5088

PDF - Publisher Version

Official URL:

Related URL:


Chandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) induces neuronal death through the Fas-mediated extrinsic apoptosis pathway. What propels this apoptosis remains unclear, although oxysterols have been reported to be key players in neurodegeneration. In our study of CHPV-infected brain samples, we observed over-expression of genes such as apolipoprotein E, Cyp46a1, Srebf-1 and Nsdhl. This backs up the hypothesis that CHPV replication demands cholesterol that is supplied by apolipoprotein E through low density lipid receptors, lipid metabolism being pivotal for viral replication. We were able to illustrate this with over-expression of low density lipid receptors in CHPV-infected neurons. An upsurge of cholesterol concentration has been observed in neurons, triggering the expression of Cyp46a1 enzyme and culminating into the conversion of cholesterol to 24(S)-hydroxycholesterol. Increased 24(S)-hydroxycholesterol concentration is toxic to neurons, propelling neuronal apoptosis through the Fas-mediated extrinsic apoptosis pathway. For the first time, perturbation of cholesterol homeostasis in brain is shown to be utilized by the viruses for both maturation and the release of its matured virions outside the cells for continuous neuropathogenesis. Chandipura virus (CHPV) increases cholesterol import through low density lipid (LDL) receptor in neurons. Cholesterol in neurons are utilized to form the CHPV envelope. Excessive accumulation of cholesterol gets converted to 24(S)-hydroxycholesterol (24(S)-OHC) by cholesterol 24-hydroxylase enzyme (encoded by Cyp46a1 gene) that induces neuronal death through apoptosis. Therapeutics aimed against cholesterol homeostasis perturbation may be an effective anti-viral strategy.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Chandipura Virus; Cholesterol Homeostasis; Neuronal Apoptosis
ID Code:112972
Deposited On:05 Jun 2018 09:45
Last Modified:05 Jun 2018 09:45

Repository Staff Only: item control page