Human respiratory syncytial virus (RSV) is an enveloped RNA-containing virus of the paramyxovirus family of Order Mononegavirales (the nonsegmented negative strand RNA viruses). RSV is the most important viral agent of pediatric respiratory tract disease worldwide. Other members of the Order include measles, mumps, rabies and Ebola viruses. The RSV genome is a single negative strand of RNA of 15,222 nucleotides that encodes 10 major mRNAs and 11 proteins, as we have shown previously. The purpose of this project is to identify the functions of the viral proteins and to reconstruct events in the viral growth cycle under conditions where they can be more readily studied. Knowledge of the functions of the proteins is important for a basic understanding of this important human pathogen and for the design of live-attenuated recombinant vaccine viruses.We previously developed an experimental system for RSV based on the intracellular coexpression and assembly of viral RNA and protein components from recombinant plasmid vectors. This involves transfecting cultured cells with plasmids which individually encode a truncated version of negative-sense genomic or positive-sense antigenomic RNA (the latter being an intermediate in RNA replication) as well as whatever mix of RSV proteins is desired. In this way, various steps in the viral replication cycle can be reconstituted, such as genome replication, gene expression, gene regulation, packaging and infection. Because each component is expressed individually, each can be manipulated individually with regard to relative amount as well as by mutagenesis for structure-function studies. - virus, respiratory tract disease, infectious disease, pediatrics, vaccines, live- attenuated viral vaccine, recombinant DNA, proteins

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000498-13
Application #
6288863
Study Section
Special Emphasis Panel (LID)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
McGivern, David R; Collins, Peter L; Fearns, Rachel (2005) Identification of internal sequences in the 3' leader region of human respiratory syncytial virus that enhance transcription and confer replication processivity. J Virol 79:2449-60
Zhang, Liqun; Bukreyev, Alexander; Thompson, Catherine I et al. (2005) Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J Virol 79:1113-24
Schomacker, Henrick; Collins, Peter L; Schmidt, Alexander C (2004) In silico identification of a putative new paramyxovirus related to the Henipavirus genus. Virology 330:178-85
Tran, Kim C; Collins, Peter L; Teng, Michael N (2004) Effects of altering the transcription termination signals of respiratory syncytial virus on viral gene expression and growth in vitro and in vivo. J Virol 78:692-9
Spann, Kirsten M; Collins, Peter L; Teng, Michael N (2003) Genetic recombination during coinfection of two mutants of human respiratory syncytial virus. J Virol 77:11201-11
Kotelkin, Alexander; Prikhod'ko, Elena A; Cohen, Jeffrey I et al. (2003) Respiratory syncytial virus infection sensitizes cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand. J Virol 77:9156-72
Zhang, Liqun; Peeples, Mark E; Boucher, Richard C et al. (2002) Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol 76:5654-66
Teng, Michael N; Collins, Peter L (2002) The central conserved cystine noose of the attachment G protein of human respiratory syncytial virus is not required for efficient viral infection in vitro or in vivo. J Virol 76:6164-71
Techaarpornkul, Sunee; Collins, Peter L; Peeples, Mark E (2002) Respiratory syncytial virus with the fusion protein as its only viral glycoprotein is less dependent on cellular glycosaminoglycans for attachment than complete virus. Virology 294:296-304
Gower, T L; Peeples, M E; Collins, P L et al. (2001) RhoA is activated during respiratory syncytial virus infection. Virology 283:188-96

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