THE MURINE CORONAVIRUS MOUSE HEPATITIS-VIRUS STRAIN A59 FROM PERSISTENTLY INFECTED MURINE CELLS EXHIBITS AN EXTENDED HOST-RANGE

In murine 17 Cl 1 cells persistently infected with murine coronavirus mouse hepatitis virus strain A59 (MHV-A59), expression of the virus re ceptor glycoprotein MHVR was markedly reduced (S. G. Sawicki, J. H. Lu , and K. V. Holmes, J. Virol 69:5535-5543, 1995). Virus isolated from. passage 600 of the persistently infected cells made smaller plaques o n 17 Cl 1 cells than did MHV-A59. Unlike the parental MHV-A59, this va riant virus also infected the BHK-21 (BHK) line of hamster cells. Viru s plaque purified on BHK cells (MHV/BHK) grew more slowly in murine ce lls than did MHV-A59 and the rate of viral RNA synthesis was lower and the development of the viral nucleocapsid (N) protein was slower than those of MHV-A59. MHV/BHK was 100-fold more resistant to neutralizati on with the purified soluble recombinant MHV receptor glycoprotein (sM HVR) than was MHV-A59. Pretreatment of 17 Cl 1 cells with anti-MHVR mo noclonal antibody CC1 protected the cells from infection with MHV-A59 but only partially protected them from. infection with MHV/BHK. Thus, although MHV/BHK could still utilize MHVR as a receptor, its interacti ons with the receptor were significantly different from those of MHV-A 59. To determine whether a hemagglutinin esterase (HF) glycoprotein th at could bind the virions to 9-O-acetylated neuraminic acid moieties o n the cell surface was expressed by MHV/BHK an in situ esterase assay was used. No expression of HE activity was detected in 17 Cl 1 cells i nfected with MHV/BHK, suggesting that this virus, like MHV-A59, bound to cell membranes via its S glycoprotein. MHV/BHK was able to infect c ell lines from many mammalian species, including murine (17 Cl 1), ham ster (BHK), feline (Fcwf), bovine (MDBK), rat (RIE), monkey (Vero), an d human (L132 and HeLa) cell lines. MHV/BHK could not infect dog kidne y (MDCK I) or swine testis (ST) cell lines. Thus, in persistently infe cted murine cell lines that express very low levels of virus receptor MHNR and which also have and may express alternative virus receptors o f lesser efficiency, there is a strong selective advantage for virus w ith altered interactions with receptor (D. S. Chen, M. Asanaka, F. S. Chen, J. E. Shivery, and M. M. C. Lai, J. Virol. 71:1688-1691, 1997; D . S. Chen, M. Asanaka, K. Yokomori, F.-I. Wang, S. E. Hwang, H.-P. Li, and M. M. C. Lai, Proc Natl. Acad. Sci. USA 92:12095-12099, 1995; P. Nedellec, G. S. Dveksler, E. Daniels, C. Turbide, B. Chow, A. A. Basil e, K. V. Holmes, and N. Beauchemin, J. Virol. 68:4525-4537, 1994). Pos sibly, in coronavirus-infected animals, replication of the virus in ti ssues that express levy levels of receptor might also select viruses w ith altered receptor recognition and extended host range.