+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Intracellular complexes of viral spike and cellular receptor accumulate during dytopathic murine coronavirus infections



Intracellular complexes of viral spike and cellular receptor accumulate during dytopathic murine coronavirus infections



Journal of Virology 72(4): 3278-3288



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 apprx1,500 molecules per cell (designated Rlo) to apprx300,000 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; Rl0 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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 008904741

Download citation: RISBibTeXText

PMID: 9525655


Related references

A role for naturally occurring variation of the murine coronavirus spike protein in stabilizing association with the cellular receptor. Journal of Virology 71(4): 3129-3137, 1997

Substitutions of conserved amino acids in the receptor-binding domain of the spike glycoprotein affect utilization of murine CEACAM1a by the murine coronavirus MHV-A59. Virology 334(1): 98-110, 2005

Increased viral titers and enhanced reactivity of antibodies to the spike glycoprotein of murine coronavirus produced by infection at pH 6. Journal Of Virological Methods. 50(1-3): 237-244, 1994

Receptor-induced conformational changes of murine coronavirus spike protein. Journal of Virology 76(23): 11819-11826, 2002

The spike protein of murine coronavirus regulates viral genome transport from the cell surface to the endoplasmic reticulum during infection. Journal of Virology 83(20): 10653-10663, 2009

Identification of spike protein residues of murine coronavirus responsible for receptor-binding activity by use of soluble receptor-resistant mutants. Journal of Virology 71(12): 9024-9031, 1997

Analysis of the receptor-binding site of murine coronavirus spike protein. Journal of Virology 70(4): 2632-2636, 1996

The S2 subunit of the murine coronavirus spike protein is not involved in receptor binding. Journal of Virology 69(11): 7260-7263, 1995

Murine coronavirus spike glycoprotein. Receptor binding and membrane fusion activities. Advances in Experimental Medicine and Biology 494: 183-192, 2001

Murine coronavirus spike glycoprotein mediates degree of viral spread, inflammation, and virus-induced immunopathology in the central nervous system. Virology 301(1): 9-20, 2002

Interaction between the spike protein of human coronavirus NL63 and its cellular receptor ACE2. Advances in Experimental Medicine and Biology 581: 281-284, 2006

Localization of neutralizing epitopes and receptor-binding site in murine coronavirus spike protein. Advances in Experimental Medicine and Biology 380: 359-365, 1995

Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system. Virology 312(2): 9-80, 2003