CONSEQUENCES OF A SUBTLE SIALIC-ACID MODIFICATION ON THE MURINE POLYOMAVIRUS RECEPTOR

Polyomaviruses are small, nonenveloped DNA tumor viruses with restrict ed host ranges, Virus binding to cell surface receptors is one determi nant of viral tropism, Although murine polyomavirus is among the best characterized viruses, little is known about the sialic acid-containin g receptor and its interaction with viral particles, By using nonradio active virus binding assays as recently described for the B-lymphotrop ic papovavirus murine polyomavirus particles were found to bind in a s aturable and noncooperative manner to 25,000 receptors per 3T6 mouse f ibroblast, The virus receptor interaction at 4 degrees C was of high a ffinity (K-d = 1.8 x 10(-11) M), very fast (k(1) = 1.7 x 10(7) M-1 s(- 1)), and stable (half-life = 38 min), Elongation of the N-acyl side ch ain of sialic acid by biosynthetic modulation with synthetic precursor analogs has been shown for other polyomaviruses to influence both sia lic acid-dependent binding and infection (O. T. Keppler, P. Stehling, M. Herrmann, H. Kayser, D. Grunow, W. Reutter, and M. Pawlita, J. Biol . Chem. 270:1308-1314, 1995). In 3T6 cells in which about one-third of the sialic acids were modified, infection and binding of polyomavirus particles were significantly reduced, The number of receptors per cel l was decreased to 18,000, with the remaining receptors displaying the same affinity as in untreated cells, Molecular modeling studies based on the three-dimensional structure of a mouse polyomavirus-sialyllact ose complex recently solved by T. Stehle and coworkers (T. Stehle, Y. W. Yan, T. L. Benjamin, and S. C. Harrison, Nature 369:160-163, 1994) were performed, They suggest that the elongation of the N-acyl side ch ain by a single methylene group leads to steric hinderence, with the p eptide backbone of a loop walling the tip of the shallow sialic acid b inding groove, This collision appears to be incompatible with function al binding, The data are taken as a basis to discuss possible features of the organization and topology of the cellular receptor for mouse p olyomavirus.