Reovirus is a member of the Reoviridae family, and is a model system for other family members, including rotavirus, which is an important human pathogen, and bluetongue virus, which has agricultural significance as a livestock pathogen. Reovirus is non-enveloped, and virus particles must penetrate the cell membrane without the benefit of membrane fusion. Membrane translocation is known to be mediated by the myristoylated outer capsid protein mu1, but the mechanism remains largely obscure. A myristoylation-defective mutant will be used to test the hypothesis that the myristoyl moiety is important for membrane penetration. In addition, using mutants that are defective at undergoing conformational transitions associated with membrane penetration, the sequence determinants of capsid rearrangement will be investigated. These experiments aim to provide a more detailed understanding of membrane translocation by non-enveloped viruses, and may illuminate strategies for fighting infection by Reoviridae family members, and non-enveloped viruses in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AI064142-01
Application #
6891982
Study Section
Special Emphasis Panel (ZRG1-IDM-L (29))
Program Officer
Hernandez, Milton J
Project Start
2005-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$31,466
Indirect Cost
Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Zhang, Lan; Agosto, Melina A; Ivanovic, Tijana et al. (2009) Requirements for the formation of membrane pores by the reovirus myristoylated micro1N peptide. J Virol 83:7004-14
Ivanovic, Tijana; Agosto, Melina A; Zhang, Lan et al. (2008) Peptides released from reovirus outer capsid form membrane pores that recruit virus particles. EMBO J 27:1289-98
Agosto, Melina A; Myers, Kimberly S; Ivanovic, Tijana et al. (2008) A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration. Proc Natl Acad Sci U S A 105:10571-6
Agosto, Melina A; Middleton, Jason K; Freimont, Elaine C et al. (2007) Thermolabilizing pseudoreversions in reovirus outer-capsid protein micro 1 rescue the entry defect conferred by a thermostabilizing mutation. J Virol 81:7400-9
Middleton, Jason K; Agosto, Melina A; Severson, Tonya F et al. (2007) Thermostabilizing mutations in reovirus outer-capsid protein mu1 selected by heat inactivation of infectious subvirion particles. Virology 361:412-25
Ivanovic, Tijana; Agosto, Melina A; Chandran, Kartik et al. (2007) A role for molecular chaperone Hsc70 in reovirus outer capsid disassembly. J Biol Chem 282:12210-9
Agosto, Melina A; Ivanovic, Tijana; Nibert, Max L (2006) Mammalian reovirus, a nonfusogenic nonenveloped virus, forms size-selective pores in a model membrane. Proc Natl Acad Sci U S A 103:16496-501