Systems Biomedicine of Rabies Delineates the Affected Signaling pathways

Abstract

The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs) in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein-protein interaction network (PPIN) of infected cells to elucidate biological signaling transduction pathways affected by rabies virus. To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets.

Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

“…Preservation of infected neurons is vital for viral dissemination (Lafon 2011). However, hijacking neurons through multiple signaling pathways (Azimzadeh Jamalkandi et al 2016) may be reflected by aberrant synaptic transmission (Fu and Jackson 2005) or ion channels dysfunctions (Iwata et al 1999) leading to rabies-associated clinical manifestations and ultimately death. Various RABV strains differently affect the homeostasis of infected neurons.…”

Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

“…The pathogenesis mechanism of HTLV‐1 stays pathless, which creates a barrier in finding an efficient diagnosis and treatment method. To this purpose, the scrutiny of pathogenesis at the transcriptomic level can untangle the intricate pathways of diseases …”

Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer

“…Of course such evidence (from bioinformatics analysis and literature) needs to be biologically validated in vitro before we can safely associate the TAB2 protein with lung cancer. Furthermore, we have to acknowledge that our analysis is focused only in the affected pathways that MinePath identified but biological networks provide much more information that can follow up research outcomes such as the identification or reconstruction of a proteinprotein interaction network [35], [36]. We also plan to provide the pipeline in the OpenBio-C workflow environment [37] as a bioinformatics pipeline proof of concept for the validity of integrating ChIP-seq and RNA-seq datasets.…”