Li H , Fan M , Liu B , Ji P , Chen Y , Zhang B , Sun Y , Huang B , Nan Y , Sun Z , Stewart JP , Hiscox JA , Zhao Q , Zhou EM .

J Virol. 2019 Mar 20. pii: JVI.02205-18. doi: 10.1128/JVI.02205-18. [Epub ahead of print]

Abstract

Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease in chickens. Due to the absence of a highly effective cell culture system, there are few reports about the interaction between avian HEV and host cells. In this study, organic anion transporting polypeptide 1A2 (OATP1A2) from the chicken liver cells was identified to interact with ap237, a truncated avian HEV capsid protein spanning amino acids 313 to 549, by the GST pull-down assay. Then, the GST pull-down and indirect ELISA assays further confirmed that the extracellular domain of OATP1A2 directly binds with ap237. The expression levels of OATP1A2 in host cells are positively correlated with the amounts of ap237 attachment and virus infection. The distribution of OATP1A2 in different tissues is consistent with avian HEV infection in vivo Finally, when the functions of OATP1A2 in the cells are inhibited by its substrates, an inhibitor or blocked by ap237 or anti-OATP1A2 sera, the attachment and infection of avian HEV of the host cells is significantly reduced. Collectively, these results displayed that for the first time, OATP1A2 interacts with the avian HEV capsid protein and can influence viral infection in host cells. The present study provided new insight to understand the process of avian HEV infection of host cells.IMPORTANCE The process of viral infection is centered around the interaction between the virus and host cells. Due to the lack of a highly effective cell culture system in vitro, there is little understanding about the interaction between avian HEV and its host cells. In this study, a total of seven host proteins were screened from chicken liver cells by a truncated avian HEV capsid protein (ap237) in which the host protein OATP1A2 interacted with ap237. Overexpression of OATP1A2 in LMH cells can promote ap237 adsorption as well as avian HEV adsorption and infection of LMH cells. When the function of OATP1A2 in the cells was inhibited by substrates or inhibitors, the attachment and infection of avian HEV significantly decreased. The distribution of OATP1A2 in different chicken tissues corresponded with the tissues of avian HEV infection. This is the first finding that OATP1A2 is involved in viral infection of host cells.