This study aims to better understand the mechanisms by which Ebola virus infects cells and causes disease. To better understand the mechanisms by which Ebola virus infects cells and causes disease. Our laboratory is interested the basic biology underlying Ebola virus pathogenesis, virus-host interactions, and inhibition of virus replication. Ebola virus is a non-segmented negative strand RNA virus with a simple genome containing seven open reading frames. The virus replication cycle begins with binding of the envelope glycoprotein, GP, to a putative cell surface receptor(s) and entry into the host cell by fusion of viral and cell membranes. Strategies to interrupt the virus life cycle can be targeted to these early entry events or to later steps in the replication cycle. Our hypothesis is that molecular events underlying Ebola GP interactions within the host contribute to preferential targeting of Ebola virus infection to specific cell types, mediate pathogenic properties of the virus, and influence immune responses generated against the virus. Our goal with these studies is to identify points in the Ebola virus replication cycle that are vulnerable antiviral and neutralization targets. We are approaching this goal with several aims, each focusing on a particular aspect of GP function.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2011
Total Cost
$901,608
Indirect Cost
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State
Country
Zip Code
Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J (2012) Ebolavirus vaccines for humans and apes. Curr Opin Virol 2:324-9
Misasi, John; Chandran, Kartik; Yang, Jin-Yi et al. (2012) Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J Virol 86:3284-92
Fabozzi, Giulia; Nabel, Christopher S; Dolan, Michael A et al. (2011) Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway. J Virol 85:2512-23
Geisbert, Thomas W; Bailey, Michael; Geisbert, Joan B et al. (2010) Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J Virol 84:10386-94
Hensley, Lisa E; Mulangu, Sabue; Asiedu, Clement et al. (2010) Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus Species. PLoS Pathog 6:e1000904
Shedlock, Devon J; Bailey, Michael A; Popernack, Paul M et al. (2010) Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms. Virology 401:228-35
Sullivan, Nancy J; Martin, Julie E; Graham, Barney S et al. (2009) Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule. Nat Rev Microbiol 7:393-400