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

Although Src activity may differ between the tumor cell line LMH and primary cells, considering the instability of the biological characteristics of different isolates and the short life span of primary cells during in vitro culture, the LMH cell line was chosen in the present study to establish a stable, experimental model for microarray assays and subsequent mechanistic studies. Given that the key host determinant of ILTV infection in the tumor cell line LMH is a well-known oncogene, it was crucial to determine whether the host Src/FAK-mediated mechanism that we found in LMH cells is also present in normal cells, especially in vivo. Hence, we first examined the effect of an Src/FAK inhibitor on ILTV replication in SPF embryos and observed an effect similar to that caused by the Src/FAK inhibitor in LMH cells ( Fig. 4 and 7) . Furthermore, during the in ovo study, we examined the histopathology of the livers of ILTV-infected chicken embryos and assayed the amount of virus transmitted to the liver. All the results support the notion that, instead of a tumor cell line-specific event, the mechanism that we identified in LMH cells is universal in normal cells and tissues. In addition, we also analyzed the only publicly available, genome-wide gene expression data for chicken embryo lung cells infected with a different virulent ILTV strain at an MOI of 0.1 (18) , which again revealed that host Src is the central regulator of the molecular network induced by ILTV infection in host cells (see Fig. S4 in the supplemental material).