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J Virol, April 1998, p. 3278-3288, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections

Pasupuleti V. Rao and Thomas M. Gallagher*

Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 60153

Received 10 September 1997/Accepted 22 December 1997

Murine hepatitis virus (MHV) infections exhibit remarkable variability in cytopathology, ranging from acutely cytolytic to essentially asymptomatic levels. In this report, we assess the role of the MHV receptor (MHVR) in controlling this variable virus-induced cytopathology. We developed human (HeLa) cell lines in which the MHVR was produced in a regulated fashion by placing MHVR cDNA under the control of an inducible promoter. Depending on the extent of induction, MHVR levels ranged from less than ~1,500 molecules per cell (designated Rlo) to ~300,000 molecules per cell (designated Rhi). Throughout this range, the otherwise MHV-resistant HeLa cells were rendered susceptible to infection. However, infection in the Rlo cells occurred without any overt evidence of cytopathology, while the corresponding Rhi cells died within 14 h after infection. When the HeLa-MHVR cells were infected with vaccinia virus recombinants encoding MHV spike (S) proteins, the Rhi cells succumbed within 12 h postinfection; Rlo cells infected in parallel were intact, as judged by trypan blue exclusion. This acute cytopathology was not due solely to syncytium formation between the cells producing S and MHVR, because fusion-blocking antiviral antibodies did not prevent it. These findings raised the possibility of an intracellular interaction between S and MHVR in the acute cell death. Indeed, we identified intracellular complexes of S and MHVR via coimmunoprecipitation of endoglycosidase H-sensitive forms of the two proteins. We suggest that MHV infections can become acutely cytopathic once these intracellular complexes rise above a critical threshold level.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153. Phone: (708) 216-4850. Fax: (708) 216-9574. E-mail: tgallag{at}luc.edu.




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