FORMATION OF INTRACELLULAR PARTICLES BY HEPATITIS-B VIRUS LARGE SURFACE PROTEIN

Hepatitis B virus small surface protein is synthesized as a transmembr ane protein of the rough endoplasmic reticulum (RER) and then buds int o the lumen in the form of subviral particles that are secreted, The c losely related large surface protein is also targeted to the RER but i s retained in a pre-Golgi compartment and cannot be secreted, It has b een assumed that the large surface protein remains as a transmembrane RER protein and hence cannot form particles, possibly because of bindi ng to a host factor on the cytosolic face of the RER membranes. We hav e reexamined this question and found the following results, (i) The re tained large surface protein is associated not with RER but, rather, w ith a more distal compartment. (ii) Electron microscopy reveals intrav esicular 20-nm particles, similar to those formed by the small surface protein, (iii) The large surface protein colocalizes with and binds t o calnexin, an ER chaperone protein, Therefore, our results indicate t hat the large surface protein is capable of budding and forming partic les, and hence its intracellular retention cannot be attributed to a c ytosolic factor, We interpret the data as evidence that the large surf ace protein is retained by virtue of interacting with calnexin, a comp onent of what is considered the quality control mechanism of the ER.