Impaired entry of soluble receptor-resistant mutants of mouse hepatitis virus into cells expressing MHVR2 receptor

Abstract

Mouse hepatitis virus (MHV) JHMV and its soluble receptor-resistant (srr) mutants, srr7, srr11, and srr18, grew and induced syncytia equally well in BHK-R1 cells expressing the MHVR1 receptor derived from MHV-susceptible BALB/c mice. In contrast, srr growth and syncytia formations were drastically reduced relative to wild-type (wt) virus in BHK-R2 cells expressing the MHVR2 receptor from MHV-resistant SJL mice. Infections by these srr mutants in BHK-R2 cells were 0.7 to 1.5 log l0 less efficient than those of wt virus. BHK cells expressing both MHVR1 and MHVR2 supported srr replication to the same extent as did BHK-R1 cells, suggesting that inefficient infection by srr mutants in BHK-R2 cells resulted from the absence of the effective receptor MHVR1. Virus-receptor binding tests failed to demonstrate a difference between the abilities of wt and srr18 to bind MHVR2. The binding of srr7 and srr11 to both MHVR1 and MHVR2 was revealed lower by two- to fourfold relative to the wt binding. The fusion activity of srr S proteins as examined by the expression with recombinant vaccinia virus was apparently lower than that of the wt S protein in BHK-R2 cells, while there was not such a remarkable difference in BHK-R1 cells. This suggests that the most likely reason for inefficient infection by mutants in BHK-R2 is impaired virus entry into cells. These observations suggest that inefficient infections in BHK-R2 cells by srr mutants occur in the absence of a functional receptor MHVR1, which plays an important role in srr entry into cells. (C) 2000 Academic Press.