It is the goal of this research to elucidate the molecular events leading to the formation of an infectious enveloped virus (the alphavirus Sindbis) from its component parts. Specifically, this research program will have four primary goals: 1) The elucidation of the types of virus protein/protein interactions and processing events essential for transport and assembly of virus components into infectious virions; 2) The identification of host functions involved in the transport and development of functional virus membrane proteins; 3) Determination of the 3-dimensional structure of Sindbis virus by X-ray crystallography; 4) The elucidation of the organization of Sindbis virus RNA and protein interactions within the nucleocapsid. In pursuing these objectives, information will be gathered which is important to understanding the mechanisms employed by cells in the production, processing and transport of cell plasma membrane proteins, as well as the molecular organization of the RNA, lipid, and protein components of an important group of human and animal pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI014710-10
Application #
3566206
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-09-01
Project End
1994-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Carleton, M; Brown, D T (1997) The formation of intramolecular disulfide bridges is required for induction of the Sindbis virus mutant ts23 phenotype. J Virol 71:7696-703
Karpf, A R; Lenches, E; Strauss, E G et al. (1997) Superinfection exclusion of alphaviruses in three mosquito cell lines persistently infected with Sindbis virus. J Virol 71:7119-23
Carleton, M; Lee, H; Mulvey, M et al. (1997) Role of glycoprotein PE2 in formation and maturation of the Sindbis virus spike. J Virol 71:1558-66
Lee, S; Owen, K E; Choi, H K et al. (1996) Identification of a protein binding site on the surface of the alphavirus nucleocapsid and its implication in virus assembly. Structure 4:531-41
Carleton, M; Brown, D T (1996) Events in the endoplasmic reticulum abrogate the temperature sensitivity of Sindbis virus mutant ts23. J Virol 70:952-9
Liu, L N; Lee, H; Hernandez, R et al. (1996) Mutations in the endo domain of Sindbis virus glycoprotein E2 block phosphorylation, reorientation of the endo domain, and nucleocapsid binding. Virology 222:236-46
Carleton, M; Brown, D T (1996) Disulfide bridge-mediated folding of Sindbis virus glycoproteins. J Virol 70:5541-7
Mulvey, M; Brown, D T (1996) Assembly of the Sindbis virus spike protein complex. Virology 219:125-32
Bowers, D F; Abell, B A; Brown, D T (1995) Replication and tissue tropism of the alphavirus Sindbis in the mosquito Aedes albopictus. Virology 212:1-12
Mulvey, M; Brown, D T (1995) Involvement of the molecular chaperone BiP in maturation of Sindbis virus envelope glycoproteins. J Virol 69:1621-7

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