Herpesviruses are responsible for several human diseases including chickenpox, shingles, oral and genital herpes, and life-threatening infections in persons with weakened immune systems. Varicella-zoster virus (VZV), like all herpesviruses, has an outer membrane that is essential for infectivity. It acquires its initial membrane upon the passage of viral capsids from the nucleus of infected cells through the inner nuclear membrane. After that, the precise mechanism by which VZV acquires its final infection-competent envelope, and the route it follows during egress from infected cells is unclear. It is known, however, that herpesvirus egress requires the golgi- dependent maturation of several virus-encoded glycoproteins. This emphasizes the critical importance of viral glycoprotein transport for herpesvirus assembly and egress. Glycoprotein B (gB), a protein represented in all herpesviruses, is thought to be vital for the normal egress of virus from infected cells. Unlike most herpesvirus membrane proteins, gB possesses a long cytoplasmic domain that has been implicated in its own intracellular transport as well as in viral egress. However, specific intracellular targeting sequences within the cytoplasmic domain gB have not been identified for any of the herpesviruses, nor is it known what impact mutations in these sequences may have on viral assembly and growth. We propose to (i) identify the specific signal sequences within the cytoplasmic domain VZV gB that are required for its intracellular transport; (ii) determine whether disruption of gB intracellular transport affects virus assembly and egress; and (iii) determine how mutations that alter the transport of gB affect VZV growth in cultured cells and in human tissue. This research may identify critical viral metabolic pathways and may ultimately lead to the development of new antiviral therapies.
| Schleiss, Mark R; Heineman, Thomas C (2005) Progress toward an elusive goal: current status of cytomegalovirus vaccines. Expert Rev Vaccines 4:381-406 |
| Heineman, Thomas C; Connolly, Patrick; Hall, Susan L et al. (2004) Conserved cytoplasmic domain sequences mediate the ER export of VZV, HSV-1, and HCMV gB. Virology 328:131-41 |
| Heineman, Thomas C; Hall, Susan L (2002) Role of the varicella-zoster virus gB cytoplasmic domain in gB transport and viral egress. J Virol 76:591-9 |
