Scientific Publications by FDA Staff

Virus Res 2006 Nov;121(2):205-14

Identification of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry.

Mpanju OM, Towner JS, Dover JE, Nichol ST, Wilson CA

Wilson CA (reprint author), Bldg 29B,Rm 2NN12,HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Div Cellular Tissue & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20892 USA Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30329 USA

Using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of Zaire ebolavirus (ZEBOV), we analyzed 15 conserved residues in the N-terminus of the filovirus glycoprotein 1 (GP1) in order to identify residues critical for cell entry. Results from infectivity assays and Western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for ZEBOV entry in vitro. We extended this observation by introduction of alanines at either position 88 or 159 of Ivory Coast Ebolavirus (CIEBOV) and observed the same phenotype. Further, we showed that introduction of each of the two mutations in a recombinant full-length clone of ZEBOV (Mayinga strain) that also carried the coding sequence for GFP could not be rescued, suggesting the mutants rendered the virus non-infectious. The two phenylalanines that are critical for both ZEBOV and CIEBOV entry are found in two linear domains of GP1 that are highly conserved among filoviruses, and thus could provide a target for rational development of broadly cross-protective vaccines or antiviral therapies.