Structure and Expression of the Paramyxovirus SV5 Genome

  • Lamb, Robert A (PD/PI)
  • Paterson, Reay G (Co-PD/PI)

Project: Research project

Project Details


DESCRIPTION (provided by applicant): The paramyxoviruses are the etiological agents of many important diseases of man and lower animals. Collectively, these viruses contribute significantly to worldwide morbidity and mortality. The focus of this study is the mechanism by which a prototype paramyxovirus, simian parainfluenza virus 5 (SV5) enters cells. The entry of enveloped viruses into cells requires the fusion of the viral envelope with a cellular membrane. The mechanism of viral-mediated membrane fusion is a topic of interest to cell biologists and structural biologists as well as those investigating the mechanism of virus entry. This is because membrane fusion is a process central in cell biology as it occurs at many stages of endocytosis and exocytosis. In addition, studies on the mechanism by which paramyxoviruses cause cell fusion are of significance for understanding the pathogenesis of human immunodeficiency virus 1. While our long-term goal is to use X-ray structural analysis to understand the molecular basis for paramyxovirus-mediated membrane fusion, we also need to use other functional approaches to identify determinants of paramyxovirus glycoproteins that are important for viral entry. We will study properties of the SV5 fusion (F) protein in six interrelated specific aims. We will analyze structure/function relationships of the SV5 F protein core trimer, which is composed of the F protein N-1 and C-1 heptad repeat regions, based on the atomic structure that we determined recently at 1.4 A resolution. We will investigate: (a) mutants that are predicted to alter core trimer stability; (b) mutants designed to investigate F protein conformation and (C) mutants designed to test properties of the fusion peptide. We will determine the mechanism of action of peptide inhibitors of SV5 fusion including: (a) determination of IC50 of peptide C-1 containing "guest site" mutations at L447 and I449 which insert into a deep cavity in the N-1
Effective start/end date7/1/015/31/06


  • National Institute of Allergy and Infectious Diseases (5 R01 AI023173-20)


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