Structural Analysis of the Genome of Respiratory Syncytial Virus

Collins, Peter Leon

Abstract

Respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral agent of pediatric respiratory tract disease worldwide. It currently lacks a licensed vaccine. RSV is a member of the paramyxovirus family of Order Mononegavirales, the nonsegmented negative strand RNA viruses, and RSV is the most complex member of the group. This large group of viruses includes important pathogens such as measles, mumps, rabies and Ebola viruses. Knowledge of the organization and expression of the RSV genome would help guide efforts to make attenuated recombinant viruses as vaccines, which is the major goal of related projects in this laboratory. We previously sequenced the 15,222-nucleotide genome of RSV, mapped its genes and its transcription signals, and analyzed its mechanism of gene expression. We currently are performing detailed mutagenic and functional analysis of the promoters and encapsidation signals at the 3 end of genomic and antigenomic (replicative intermediate) RNA. - Virus, vaccine, live- attenuated viral vaccine, pediatrics, infectious disease, respiratory tract disease, recombinant DNA

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000368-17
• Application #: 6288840
• Study Section: Special Emphasis Panel (LID)
• Support Year: 17
• Fiscal Year: 1999

Institution

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

Publications

Melendi, Guillermina A; Zavala, Fidel; Buchholz, Ursula J et al. (2007) Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus. J Virol 81:11461-7

Buchholz, Ursula J; Nagashima, Kunio; Murphy, Brian R et al. (2006) Live vaccines for human metapneumovirus designed by reverse genetics. Expert Rev Vaccines 5:695-706

Biacchesi, Stephane; Pham, Quynh N; Skiadopoulos, Mario H et al. (2006) Modification of the trypsin-dependent cleavage activation site of the human metapneumovirus fusion protein to be trypsin independent does not increase replication or spread in rodents or nonhuman primates. J Virol 80:5798-806

Biacchesi, Stephane; Skiadopoulos, Mario H; Yang, Lijuan et al. (2005) Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression. J Virol Methods 128:192-7

Buchholz, Ursula J; Biacchesi, Stephane; Pham, Quynh N et al. (2005) Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: effects on RNA synthesis, attenuation, and immunogenicity. J Virol 79:6588-97

Pham, Quynh N; Biacchesi, Stephane; Skiadopoulos, Mario H et al. (2005) Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo. J Virol 79:15114-22

Biacchesi, Stephane; Skiadopoulos, Mario H; Yang, Lijuan et al. (2004) Recombinant human Metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. J Virol 78:12877-87

Biacchesi, Stephane; Skiadopoulos, Mario H; Tran, Kim C et al. (2004) Recovery of human metapneumovirus from cDNA: optimization of growth in vitro and expression of additional genes. Virology 321:247-59

Buchholz, Ursula J; Bukreyev, Alexander; Yang, Lijuan et al. (2004) Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci U S A 101:9804-9

Biacchesi, Stephane; Skiadopoulos, Mario H; Boivin, Guy et al. (2003) Genetic diversity between human metapneumovirus subgroups. Virology 315:1-9