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Permeabilization of the plasma membrane by Ebola virus GP2

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Abstract

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.

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Acknowledgments

We thank the members of the Harty lab for insightful comments, and Shiho Irie for technical support. This work was supported by NIH grant AI46499 to R.N.H.

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Authors and Affiliations

  1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA, 19104-6049, USA

    Ziying Han, Jillian M. Licata & Ronald N. Harty

  2. Virology Division, United States Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD, 21702-5011, USA

    Jason Paragas

Authors
  1. Ziying Han
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  2. Jillian M. Licata
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  3. Jason Paragas
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  4. Ronald N. Harty
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Correspondence to Ronald N. Harty.

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Han, Z., Licata, J.M., Paragas, J. et al. Permeabilization of the plasma membrane by Ebola virus GP2. Virus Genes 34, 273–281 (2007). https://doi.org/10.1007/s11262-006-0009-4

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  • DOI: https://doi.org/10.1007/s11262-006-0009-4

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