THE EXTRACELLULAR DOMAIN OF LA-CROSSE VIRUS G1 FORMS OLIGOMERS AND UNDERGOES PH-DEPENDENT CONFORMATIONAL-CHANGES

The La Crosse virus G1 glycoprotein plays a critical role in virus bin ding to susceptible cells and in the subsequent fusion of viral and ce llular membranes. A soluble form of the G1 glycoprotein (sG1) prepared in a recombinant baculovirus system mimics the cell-binding pattern o f La Crosse virus and inhibits La Crosse virus infection (A. Pekosz at al., Virology 214, 339-348, 1995), presumably by competing for a cell ular receptor, a finding that implies that sG1 can perform some functi ons absent G2, the smaller of the two bunyavirus glycoproteins, We hav e performed experiments to determine whether sG1 is present as an olig omer and whether it undergoes the conformational changes associated wi th fusion (F. Gonzalez-Scarano, Virology 140, 209-216, 1985). Our resu lts indicate that both sG1 and native G1 undergo similar changes in co nformation after exposure to an acidic environment, as detected by rea ctivity with monoclonal antibodies. Furthermore, using chemical cross- linking, both proteins were detected as oligomers (most likely dimers) . Sucrose density gradient analysis of sG1 verified that it was presen t in monomeric and oligomeric forms. These results demonstrate that th e isolated G1 glycoprotein can undergo a pH-dependent change in confor mation in the absence of its transmembrane and cytoplasmic tail domain s and that the extracellular portion of the glycoprotein can oligomeri ze. (C) 1996 Academic Press, Inc.