Formation of the herpes simplex virus (HSV) envelope, and egress of enveloped virions from cells, is critical for the production of infectious particles and the spread of disease. Unfortunately, little is know of how HSV capsids and tegument proteins refashion cell membranes into envelopes. Similarly, the identity of the cytoplasmic organelles utilized for viral exocytosis remains obscure. Our working model is that HSV capsids acquire their final envelope in the cell cytoplasm by attaching to the surface of the Golgi apparatus or endosomes, then budding into them. Using novel assay techniques developed in this laboratory, we will purify then establish the identity and function of cytoplasmic organelles utilized for HSV envelopment. The mechanism of association of capsids and tegument proteins with the surface of these organelles, the first step in viral envelopment, will then be determined. Finally, the interaction of capsids with cytoplasmic compartments will be visualized in living cells by imaging the trafficking of Green Fluorescent Protein tagged capsids during a single, synchronized wave of assembly. Information obtained from this study will help in the design of agents able to interfere with HSV envelopment, thus reducing the virulence of this serious human pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038265-07
Application #
6510600
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Beisel, Christopher E
Project Start
1996-03-01
Project End
2006-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
7
Fiscal Year
2002
Total Cost
$292,542
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Shanda, Sara K; Wilson, Duncan W (2008) UL36p is required for efficient transport of membrane-associated herpes simplex virus type 1 along microtubules. J Virol 82:7388-94
Mukhopadhyay, Aparna; Lee, Grace E; Wilson, Duncan W (2006) The amino terminus of the herpes simplex virus 1 protein Vhs mediates membrane association and tegument incorporation. J Virol 80:10117-27
Lee, Grace E; Murray, John W; Wolkoff, Allan W et al. (2006) Reconstitution of herpes simplex virus microtubule-dependent trafficking in vitro. J Virol 80:4264-75
Chi, Jung Hee I; Harley, Carol A; Mukhopadhyay, Aparna et al. (2005) The cytoplasmic tail of herpes simplex virus envelope glycoprotein D binds to the tegument protein VP22 and to capsids. J Gen Virol 86:253-61
Kamen, Douglas E; Gross, Sarah T; Girvin, Mark E et al. (2005) Structural basis for the physiological temperature dependence of the association of VP16 with the cytoplasmic tail of herpes simplex virus glycoprotein H. J Virol 79:6134-41
Lee, Grace E; Church, Geoffrey A; Wilson, Duncan W (2003) A subpopulation of tegument protein vhs localizes to detergent-insoluble lipid rafts in herpes simplex virus-infected cells. J Virol 77:2038-45
Gross, Sarah T; Harley, Carol A; Wilson, Duncan W (2003) The cytoplasmic tail of Herpes simplex virus glycoprotein H binds to the tegument protein VP16 in vitro and in vivo. Virology 317:1-12
Dasgupta, A; Wilson, D W (2001) Evaluation of the primary effect of brefeldin A treatment upon herpes simplex virus assembly. J Gen Virol 82:1561-7
Harley, C A; Dasgupta, A; Wilson, D W (2001) Characterization of herpes simplex virus-containing organelles by subcellular fractionation: role for organelle acidification in assembly of infectious particles. J Virol 75:1236-51
Chi, J H; Wilson, D W (2000) ATP-Dependent localization of the herpes simplex virus capsid protein VP26 to sites of procapsid maturation. J Virol 74:1468-76

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