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

Blocking FAK activity through the use of PF573228 exacerbated the ILTV CPE (Fig. 7A) . The level of apoptosis induced by ILTV in cells pretreated with PF5732228 was nearly 2-fold higher than that in DMSO-treated cells at 2 dpi (Fig. 7B ). In addition, ILTV replication was reduced by approximately 79% following PF573228 treatment (Fig. 7C, bottom) , as assayed by qPCR when all the ILTV-infected cells were dead (Fig. 7C, top) . Treatment with PF573228 in ovo, which did not induce embryo death by itself but which killed embryos in combination with ILTV infection during the observation period (data not shown), significantly reduced the level of virus production in allantoic fluid (Fig. 7D) and CAMs (Fig. 7E) . Histopathological examinations of slides with liver tissue stained with H&E showed more severe hepatic tissue necrosis in inoculated livers upon cotreatment with PF5732228 (with ILTV infection only, tissue necrosis was absent in four inoculated livers and mild in two; with ILTV infection and PF5732228 treatment, tissue necrosis was found to be mild in one inoculated liver, moderate in three inoculated livers, and severe in two inoculated livers) (Fig. 7F) . Correspondingly, a significant reduction of virus replication was observed in embryos inoculated with PF5732228 (Fig. 7G) . Collectively, our in ovo and in vitro data presented above support the notion that FAK activation is indispensable for Src regulation of ILTV infection.