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

I nfectious laryngotracheitis (ILT) is a major respiratory disease of chickens that is induced by avian ILT herpesvirus (ILTV; also known as gallid herpesvirus 1). ILTV belongs to the Iltovirus genus within the Herpesviridae family. Infection with ILTV can induce a mild to severe upper respiratory tract disease in chickens, depending on the virulence of the virus, and it causes large economic losses to the poultry industry worldwide annually. Vaccination using live attenuated virus has been the most commonly used method to control ILT outbreaks since the mid-20th century. Vaccination infects naive chickens with live attenuated virus, thereby establishing latent viral carriers; however, it is not recommended that this vaccine be used in regions where ILT outbreaks are absent (1) (2) (3) (4) . The majority of currently used live attenuated virus vaccines can induce successful protection in chickens (5) . New outbreaks of ILT are continually being identified in many countries, especially in regions where live attenuated vaccines have been extensively administered (6) . A growing body of evidence from molecular typing data collected worldwide has revealed that the currently used live attenuated vaccine strains could generate, via recombination, a virulent virus that could be the cause of current outbreaks (7) (8) (9) (10) (11) (12) . Increasing concerns regarding the biosafety of live attenuated ILTV vaccines have triggered the development of recombinant vaccines using viral vectors, and these have been released in some countries (6) . However, none of the currently available recombinant vaccines are able to clear latent virus from an infected host. As a consequence, a residual latent infection can induce new outbreaks under certain conditions when host immunity is compromised, such as under stress and at the onset of egg laying (13, 14) . Therefore, novel strategies that are independent of the host immune system, such as tighter farm biosecurity and anti-ILTV breeding, are required to control ILT outbreaks. It is hoped that these new strategies that are being developed will improve the control of ILT and reduce the extensive use of live attenuated virus as vaccines.