Phenylalanines at positions 88 and 159 of Ebolavirus envelope glycoprotein differentially impact envelope function.
The envelope glycoprotein (GP) of Ebolavirus (EBOV) mediates viral entry into host cells. Through mutagenesis, we and other groups reported that two phenylalanines at positions 88 and 159 of GP are critical for viral entry. However, it remains elusive which steps of viral entry are impaired by F88 or F159 mutations and how. In this study, we further characterized these two phenylalanines through mutagenesis and examined the impact on GP expression, function, and structure. Our data suggest that F159 plays an indirect role in viral entry by maintaining EBOV GP's overall structure. In contrast, we did not detect any evidence for conformational differences in GP with F88 mutations. The data suggest that F88 influences viral entry during a step after cathepsin processing, presumably impacting viral fusion.
Ou
Wu
W
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
King
Harlan
H
Delisle
Josie
J
Shi
Dashuang
D
Wilson
Carolyn A
CA
D000818:Animals; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000737:chemistry* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000502:physiology; D010649:Phenylalanine; D013329:Structure-Activity Relationship; D013820:Thermolysin / Q000502:physiology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology
D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D010649:Phenylalanine; D013820:Thermolysin