PI3K-Akt pathway mediated antiviral mechanism in silkworm Antheraea mylitta.

Abstract

Bombyx mori nucleopolyhedrosis virus (BmNPV) is a highly pathogenic virus to domestic silkworm Bombyx mori, often causing severe economic losses to silk industry. Interestingly, there are no documented reports of NPV infection in the wild silkworm Antheraea mylitta. Analysis of gene expression datasets and comparative genomic analysis of sequence datasets from B. mori and A. mylitta was undertaken to unravel the potential immune-related proteins and immune pathways involved. The B. mori silkworm races Sarupat and CSR-2 which are resistant and susceptible to BmNPV respectively were selected and challenged with virus to study BmNPV resistance related genes and their expression profile. The genes were filtered to isolate membrane proteins, their sequences were retrieved from UniProt and were compared against A. mylitta using BLASTp to search for similarity. Major proteins were putative defence proteins. Further, KEGG database was used to check for the presence of differentially regulated proteins in certain metabolic pathways. The analysis of the pathways was carried out using cytoscape software based on betweeness centrality and stress. The PI3K-Akt pathway was found to be the hub of all signals triggered during the course of NPV infection. We analyzed how the NPV infection modulates PI3K-Akt signaling by gene expression studies of the key regulator of the pathway i.e. Akt using real-time PCR in A. mylitta. A significant upregulation of Akt expression from 72h post infection reaching its peak with a 2.30 fold change at 120h pi clearly indicates an enhanced level of immune response in host towards the viral infection.