title: Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer.
abstract: The hantavirus membrane fusion process is mediated by the Gc envelope glycoprotein from within endosomes. However, little is known about the specific mechanism that triggers Gc fusion activation, and its pre- and post-fusion conformations. We established cell-free in vitro systems to characterize hantavirus fusion activation. Low pH was sufficient to trigger the interaction of virus-like particles with liposomes. This interaction was dependent on a pre-fusion glycoprotein arrangement. Further, low pH induced Gc multimerization changes leading to non-reversible Gc homotrimers. These trimers were resistant to detergent, heat and protease digestion, suggesting characteristics of a stable post-fusion structure. No acid-dependent oligomerization rearrangement was detected for the trypsin-sensitive Gn envelope glycoprotein. Finally, acidification induced fusion of glycoprotein-expressing effector cells with non-susceptible CHO cells. Together, the data provide novel information on the Gc fusion trigger and its non-reversible activation involving lipid interaction, multimerization changes and membrane fusion which ultimately allow hantavirus entry into cells.
authors: Molecular Virology Laboratory, Fundación Ciencia & Vida, Av. Zanartu 1482, Santiago, Chile.
authors: Rodrigo
authors: R
authors: Acuña
authors: Molecular Virology Laboratory, Fundación Ciencia & Vida, Av. Zanartu 1482, Santiago, Chile.
authors: Eduardo A
authors: EA
authors: Bignon
authors: Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, 8093 Zurich, Switzerland.
authors: Roberta
authors: R
authors: Mancini
authors: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors: Pierre-Yves
authors: PY
authors: Lozach
authors: Facultad de Ciencias Biologicas, Universidad Andres Bello, República 275, Santiago, Chile.|Molecular Virology Laboratory, Fundación Ciencia & Vida, Av. Zanartu 1482, Santiago, Chile.
authors: Nicole D
authors: ND
authors: Tischler
mesh_terms: D011992:Endosomes / Q000737:chemistry / Q000821:virology; D006476:Orthohantavirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018778:Hantavirus Infections / Q000821:virology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D014759:Viral Envelope Proteins