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 vaccine or effective antiviral therapy. RSV is in Family Paramyxoviridae of Order Mononegavirales, the nonsegmented negative strand RNA viruses or mononegaviruses, and 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 for use as vaccines, which is the major goal of related projects in this laboratory. It also would provide further insight into this important virus group. Previous studies identified the complete sequence of RSV genomic RNA and mapped its genes. We are continuing the analysis to characterize cis-acting signals in detail.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000368-18
• Application #: 6431555
• Study Section: (LID)
• Support Year: 18
• Fiscal Year: 2000

Institution

• Name: Niaid Extramural Activities
• 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