INTRACELLULAR-TRANSPORT OF THE GLYCOPROTEINS GE AND GI OF THE VARICELLA-ZOSTER VIRUS - GE ACCELERATES THE MATURATION OF GI AND DETERMINES ITS ACCUMULATION IN THE TRANS-GOLGI NETWORK

The varicella-zoster virus (VZV) is the etiological agent of two diffe rent human pathologies, chickenpox (varicella) and shingles (zoster), This alphaherpesvirus is believed to acquire its lipidic envelope in t he trans-Golgi network (TGN), This is consistent with previous data sh owing that the most abundant VZV envelope glycoprotein gE accumulates at steady-state in this organelle when expressed from cloned cDNA. In the present study, we have investigated the intracellular trafficking of gI, another VZV envelope glycoprotein. In transfected cells, this p rotein shows a very slow biosynthetic transport to the cell surface wh ere it accumulates. However, upon co-expression of gE, gI experiences a dramatic increase in its exit rate from the endoplasmic reticulum, i t accumulates in a sialyltransferase-positive compartment, presumably the TGN, and cycles between this compartment and the cell surface. Thi s differential behavior results from the ability of gE and gI to form a complex in the early stages of the biosynthetic pathway whose intrac ellular traffic is exclusively determined by the sorting information i n the tail of gE, Thus, gI provides the first example of a molecule lo calized to the TGN by means of its association with another TGN protei n. We also show that, during the early stages of VZV infection, both p roteins are also found in the TGN of the host cell. This suggests the existence of an intermediate stage during VZV biogenesis in which the envelope glycoproteins, transiently arrested in the TGN, could promote the envelopment of newly synthesized nucleocapsids into this compartm ent and, therefore, the assembly of infective viruses.