IS THE 110K GLYCOPROTEIN THE ONLY RECEPTOR FOR MEV AND DOES ITS EXPRESSION DETERMINE SPECIES SPECIFICITY? Kathryn V. Holmes 1 , Richard K. Williams 1 , Christine B. Cardellichio 1 , Susan R. compton 1 , Charles B. Stephensen 1 , stuart W. snyderl, Mark F. Frana 1 , Gui-Sen Jiang 1 , Abigail smith2, and Robert L. Knobler 3 1Un iformed Services University of the Health Sciences, Bethesda, MD 20814, 2 Ya le University School of Medicine, New Haven, CT 06510, and 3Thomas Jefferson Medical College, Philadelphia PA 19107 INTRODUCTION Coronaviruses exhibit strong tissue tropisms and species specificities, and the molecular mechanisms for these tropisms are of considerable interest. For mouse hepatitis virus, strain A59 (MHV-A59), a solid phase assay was developed to detect binding of virions to plasma membranes from normal target tissues of susceptible mice (1). Using a virus overlay protein blot assay, MEV-A59 was shown to bind specifically to a 100 to 110K protein from liver or intestine membranes of MEV-susceptible BALB/c mice. The specificity of virus binding was demonstrated by the observations that other enterotropic murine viruses did not bind to the same membrane protein and that MEV-A59 did not bind to any proteins from intestine or hepatocyte membranes from SJL/J mice, which are highly resistant to infection with MHV-A59 (2,3). Thus, SJL/J mice may be resistant to infection with MHV- A59 because the virus fails to bind to its normal target tissues, possibly because the virus-binding moiety is absent from the SJL/J plasma membranes. The present study was undertaken to determine whether the tissue tropism and species specificity of MEV are determined by the expression of the 110K protein which serves as the receptor for MHV-A59. Coronaviruses and Their Diseases Edited by D. Cavanagh and T.D.K. Brown Plenum Press, New York, 1990 37