Permeabilization of the plasma membrane by Ebola virus GP2.
The glycoprotein (GP) of Ebola virus (EBOV) is a multifunctional protein known to play a role in virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. EBOV GP is synthesized as a precursor which is subsequently cleaved to yield two disulfide-linked subunits: GP1 (surface-exposed [SU] subunit) and GP2 (membrane-anchored [TM] subunit). We sought to determine the effect of membrane-anchored GP2 protein expression on the integrity of host cell lipid membranes. Our findings indicated that: (i) expression of GP2 enhanced membrane permeability to hygromycin-B (hyg-B), (ii) the transmembrane (TM) domain of GP2 was essential for enhanced membrane permeability, (iii) amino acids (aa) 667ALF669 within the TM region of GP2 were important for enhanced membrane permeability, and (iv) EBOV infected cells were more permeable to hyg-B than mock infected cells. Together, these data suggest that the TM region of GP2 modifies the permeability of the plasma membrane. These findings may have important implications for GP-induced cell damage and pathogenesis of EBOV infection.
Han
Ziying
Z
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104-6049, USA.
Licata
Jillian M
JM
Paragas
Jason
J
Harty
Ronald N
RN
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006921:Hygromycin B / Q000494:pharmacology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D011993:Recombinant Fusion Proteins; C075080:S10 protein, Bluetongue virus; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C113189:envelope glycoprotein, Ebola virus; D020126:Brefeldin A; D006921:Hygromycin B