Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1

Siying Ye; Chris Cowled; Cheng-Hon Yap; John Stambas

reported every year. In addition to constant seasonal outbreaks, highly pathogenic avian influenza 45 (HPAI) strains, such as H5N1, remain an ongoing pandemic threat with recent WHO figures showing 46 454 confirmed laboratory infections and a mortality rate of 53%. It is important to note that humans 47 have very little pre-existing immunity towards avian influenza virus strains. Moreover, there is no 48 commercially available human H5N1 vaccine. Given the potential for H5N1 viruses to trigger a 49 pandemic (1, 2), there is an urgent need to develop novel therapeutic interventions to combat known 50 deficiencies in our ability to control outbreaks. Current seasonal influenza virus prophylactic and 51 therapeutic strategies involve the use of vaccination and antivirals. Vaccine efficacy is highly variable 52 as evidenced by a particularly severe 2017/18 epidemic and frequent re-formulation of the vaccine is 53 required to combat ongoing mutations in the influenza virus genome. In addition, antiviral resistance 54 has been reported for many circulating strains, including the avian influenza H7N9 virus that emerged 55 in 2013 (3, 4) . Influenza A viruses have also been shown to target and hijack multiple host cellular 56 pathways to promote survival and replication (5, 6). As such, there is increasing evidence to suggest 57 that targeting host pathways will influence virus replication, inflammation, immunity and pathology (6, 58 7). Alternative intervention strategies based on modulation of the host response could be used to 59 supplement the current prophylactic and therapeutic protocols. 60