Mouse hepatitis virus strain JHM infects a human hepatocellular carcinoma cell line

Mouse hepatitis virus (MHV) strain JHM is a coronavirus that causes encepha litis and demyelination in susceptible rodents. The known receptors for MHV are all members of the carcinoembryonic antigen family. Although human for ms of the MHV receptor can function as MHV receptors in some assays, no hum an cell line has been identified that can support wild-type MHV infection. Here we describe the infection of a human hepatocellular carcinoma cell lin e, HuH-7, with MHV. HuH-7 cells were susceptible to strains JHM-DL and JHM- DS, yielding virus titers nearly identical to those seen in mouse DBT cells . In contrast, HuH-7 cells were only marginally susceptible or completely r esistant to infection by other MHV strains, including A59. JHM produced a s trong cytopathic effect in HuH-7 cells with the formation of round plaques. Studies of various recombinant viruses between JHM and A59 strains suggest ed that the ability of JHM to infect HuH-7 cells was determined by multiple viral genetic elements. Blocking the viral spike (S) protein with a neutra lizing antibody or a soluble form of the MHV receptor inhibited infection o f HuH-7 cells, suggesting that infection is mediated through the S protein. Transfection with the prototype mouse receptor, biliary glycoprotein, rend ered HuH-7 cells susceptible to infection by other MHV strains as well, sug gesting that JHM uses a receptor distinct from the classical MHV receptor t o infect HuH-7 cells. Possible implications for human disease are discussed . (C) 1999 Academic Press.