Protein Trafficking and Membrane Biology During Viral Infection
Herpes viruses cause many human diseases, including blindness, birth defects, diseases of the peripheral and central nervous system and several forms of cancer. Production of an infectious viral particle, and thus the spread of disease, is critically dependent upon assembly of the herpes virus envelope, a lipid membrane derived from the infected host cell. Construction of this biological membrane involves the targeting of a set of virally-encoded membrane proteins to a particular cytoplasmic organelle, followed by binding of the viral capsid. Budding of the capsid through the membrane, followed by a "pinching off" fusion event generates a sealed, mature envelope with its own unique subset of membrane proteins.
We are dissecting the molecular machinery used to carry out these targeting, budding and scission events by a combination of biochemical and molecular genetic approaches. The processes of viral assembly and envelope biogenesis are being studied using novel synchronized virus assembly assays, and we have recently made several unexpected and exciting discoveries concerning the mechanism of Herpes capsid maturation (1, 2, 3, 4). Furthermore, we have just succeeded in isolating the intracellular compartments which Herpes simplex virus uses to assemble within then traffic out of infected cells (5) and have begun to identify which proteins are used by the virus to refashion these cellular organelles into envelopes. Better understanding of the events which accompany Herpes virus assembly are critical for the future development of specific anti-viral drugs.
1. Church, G.A. and Wilson, D.W. (1997) Study of Herpes Simplex Virus Maturation During a Synchronous Wave of Assembly. J. Virol. 71, 3603-3612.
2. Church, G.A., Dasgupta, A. and Wilson, D.W. (1998) Herpes Simplex Virus DNA packaging without measurable DNA Synthesis. J. Virol. 72, 2745-2751.
3. Dasgupta, A., Wilson, D.W. (1999) ATP depletion blocks Herpes Simplex Virus DNA packaging and capsid maturation. J. Virol. 73, 2006-2015.
4. Chi, J., Wilson, D.W. (2000) ATP-dependent localization of the Herpes Simplex Virus capsid protein VP26 to sites of procapsid maturation. J. Virol. 74, 1468-1476.
5. Harley, C.A., Dasgupta, A. and Wilson, D.W. (2001) Characterization of Herpes simplex virus containing organelles by subcellular fractionation. J. Virol. 75, 1236-1251.