Roles of Rsv Proteins in Host Immunity and Molecular Approaches to Vaccine Design

Collins, P L.

Abstract

The purpose of this project is to produce infectious RSV from cDNA. This would make it possible to produce and characterize attenuated strains by direct genetic engineering. To date, we have successfully """"""""rescued"""""""" a cDNA-encoded genome analog which is 49.3% of full-length and includes a foreign reporter gene under the control of RSV transcriptive signals. Standard infectious RSV was used as helper to provide proteins to complement the cDNA-encoded genome analog. This analog was packaged into infectious particles and was passaged five times in culture with undiminished efficiency. This provides support for the idea that a complete, nondefective cDNA-encoded genome can be rendered biologically active so as to yield infectious virus. Work towards rescuing a complete infectious virus is described.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000372-12
• Application #: 3746528
• Support Year: 12
• Fiscal Year: 1994

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Buchholz, Ursula J; Ward, Jerrold M; Lamirande, Elaine W et al. (2009) Deletion of nonstructural proteins NS1 and NS2 from pneumonia virus of mice attenuates viral replication and reduces pulmonary cytokine expression and disease. J Virol 83:1969-80

Munir, Shirin; Le Nouen, Cyril; Luongo, Cindy et al. (2008) Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. J Virol 82:8780-96

Collins, Peter L; Graham, Barney S (2008) Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol 82:2040-55

Chapman, Joanna; Abbott, Elizabeth; Alber, Dagmar G et al. (2007) RSV604, a novel inhibitor of respiratory syncytial virus replication. Antimicrob Agents Chemother 51:3346-53

Krempl, Christine D; Wnekowicz, Anna; Lamirande, Elaine W et al. (2007) Identification of a novel virulence factor in recombinant pneumonia virus of mice. J Virol 81:9490-501

Vallbracht, Simone; Jessen, Birthe; Mrusek, Sonja et al. (2007) Influence of a single viral epitope on T cell response and disease after infection of mice with respiratory syncytial virus. J Immunol 179:8264-73

Harker, James; Bukreyev, Alexander; Collins, Peter L et al. (2007) Virally delivered cytokines alter the immune response to future lung infections. J Virol 81:13105-11

Chi, Bo; Dickensheets, Harold L; Spann, Kirsten M et al. (2006) Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus. J Virol 80:5032-40

Bukreyev, Alexander; Serra, Maria Elina; Laham, Federico R et al. (2006) The cysteine-rich region and secreted form of the attachment G glycoprotein of respiratory syncytial virus enhance the cytotoxic T-lymphocyte response despite lacking major histocompatibility complex class I-restricted epitopes. J Virol 80:5854-61

Kotelkin, Alexander; Belyakov, Igor M; Yang, Lijuan et al. (2006) The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response. J Virol 80:5958-67