Kaposi’s sarcoma: a computational approach through protein–protein interaction and gene regulatory networks analysis

Abstract

Interactomic data for Kaposi's Sarcoma Associated Herpes virus (KSHV)-the causative agent of vascular origin tumor called Kaposi's sarcoma-is relatively modest to date. The objective of this study was to assign functions to the previously uncharacterized ORFs in the virus using computational approaches and subsequently fit them to the host interactome landscape on protein, gene, and cellular level. On the basis of expression data, predicted RNA interference data, reported experimental data, and sequence based functional annotation we also tried to hypothesize the ORFs role in lytic and latent cycle during viral infection. We studied 17 previously uncharacterized ORFs in KSHV and the host-virus interplay seems to work in three major functional pathways-cell division, transport, metabolic and enzymatic in general. Studying the host-virus crosstalk for lytic phase predicts ORF 10 and ORF 11 as a predicted virus hub whereas PCNA is predicted as a host hub. On the other hand, ORF31 has been predicted as a latent phase inducible protein. KSHV invests a lion's share of its coding potential to suppress host immune response; various inflammatory mediators such as IFN-γ, TNF, IL-6, and IL-8 are negatively regulated by the ORFs while Il-10 secretion is stimulated in contrast. Although, like any other computational prediction, the study requires further validation, keeping into account the reproducibility and vast sample size of the systems biology approach the study allows us to propose an integrated network for host-virus interaction with good confidence. We hope that the study, in the long run, would help us identify effective dug against potential molecular targets.

Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies

“…66,67,69,71,77 KSHV LATENCY, INFLAMMATION, AND COX-2 KSHV latency is proposed to be a symphony of wellorchestrated interactions between viral and host proteins leading to the transformation of infected cells for viral survival through successful genome replication and immune evasion. 70,[78][79][80][81] The host and viral protein interactions initially established by KSHV infection for survival through the establishment and maintenance of latency progress pathologically as KS and PEL under conditions of persistent selective pressures such as AIDS related or transplant associated immune suppression. 70,[79][80][81] The decrease in the incidence of KS post-HAART therapy in AIDS patients is suggestive of this scenario.…”

Identification of Synchronized Role of Transcription Factors, Genes, and Enzymes in Arabidopsis thaliana under Four Abiotic Stress Responsive Pathways

“…The statistical probability was counted following the methods mentioned by Zaman et al [21]. The data was modified as a suitable input file for Gene Cluster 3.0 functional clustering tool.…”

Herpesviruses and Their Host Cells: A Successful Liaison

“…Computational biology approaches Generation of integrated networks for virus (KSHV)host interactions analysing sequence-based functional annotation and expression, RNAi-and experimental data [58] Classical loss of function/gain of function analyses Determination of the role of THY-1 in HCMV infection via downregulation, antibody block, knockout and overexpression [59] Classical protein-protein interaction analyses like yeast two hybrid screens Identification of cellular interaction partners of HSV-1 proteins by a genome-wide virus-host protein interaction screen [60] Integrative genome-wide approaches like highthroughput RNAi screens…”