ABSTRACT Varicella-zoster virus (VZV) is enveloped in the trans -Golgi network (TGN). Here we report that glycoprotein I (gI) is required within the TGN for VZV envelopment. Enveloping membranous TGN cisternae were microscopically identified in cells infected with intact VZV. These sacs curved around, and ultimately enclosed, nucleocapsids. Tegument coated the concave face of these sacs, which formed the viral envelope, but the convex surface was tegument-free. TGN cisternae of cells infected with VZV mutants lacking gI (gI Δ ) or its C (gI ΔC )- or N-terminal (gI ΔN )-terminal domains were uniformly tegument coated and adhered to one another, forming bizarre membranous stacks. Viral envelopment was compromised, and no virions were delivered to post-Golgi structures. The TGN was not gI-immunoreactive in cells infected with the gI Δ or gI ΔN mutants, but it was in cells infected with gI ΔC (because the ectodomains of gI and gE interact). The presence in the TGN of gI lacking a C-terminal domain, therefore, was not sufficient to maintain enveloping cisternae. In cells infected with intact VZV or with gI Δ , gI ΔN , or gI ΔC mutants, ORF10p immunoreactivity was concentrated on the cytosolic face of TGN membranes, suggesting that it interacts with the cytosolic domains of glycoproteins. Because of the gE-gI interaction, cotransfected cells that expressed gE or gI were able to target truncated forms of the other to the TGN. Our data suggest that the C-terminal domain of gI is required to segregate viral and cellular proteins in enveloping TGN cisternae.

Wang, Z.-H., Gershon, M. D., Lungu, O., Zhu, Z., Mallory, S., Arvin, A. M., & Gershon, A. A. (2001). Essential Role Played by the C-Terminal Domain of Glycoprotein I in Envelopment of Varicella-Zoster Virus in the trans -Golgi Network: Interactions of Glycoproteins with Tegument. Journal of Virology, 75(1), 323–340.