Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

Li, Hai; Wang, Fengjie; Han, Zongxi; Gao, Qi; Li, Huixin; Shao, Yuhao; Sun, Nana; Liu, Shengwang

To determine the central modulator of the molecular network in LMH cells after ILTV infection, we analyzed the functional connections between the proteins encoded by the 608 significant genes using STRING software with the default settings. The protein-protein interaction network was visualized by use of the Cytoscape program (47) , with the layout of group attributes being done according to the degree of connectivity of the nodes (Fig. 2D ). Each green rectangle represents a protein whose mRNA expression was altered by ILTV infection, and these are arranged in order of their functional connectivity to the other proteins in Fig. 2D , with the most highly connected proteins being on the top line and the least connected ones being at the bottom of Fig. 2D . Most of these nodes were directly or indirectly connected to Src, plasminogen (PLG), and serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1), indicating that these three factors were the central regulators. PLG and SERPINC1 were downregulated by ILTV infection, while Src was upregulated ( Src is a key determinant of ILTV virulence and replication in LMH cells. In ILTV-infected LMH cells, Src phosphorylation was greatly increased, although there was only a minor change in the Src protein level (Fig. 3A) .