title: Evidence that Processing of the Severe Fever with Thrombocytopenia Syndrome Virus Gn/Gc Polyprotein Is Critical for Viral Infectivity and Requires an Internal Gc Signal Peptide.
abstract: The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable. Moreover, we show that expression of Gn or Gc alone is not sufficient for host cell entry while particles bearing both proteins are infectious, and we provide evidence that Gn facilitates Golgi transport and virion incorporation of Gc. Collectively, these results suggest that signal peptidase liberates mature Gc from the Gn/Gc precursor and that this process is essential for viral infectivity and thus constitutes a potential target for antiviral intervention.
authors.affiliation: Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Plegge
authors.affiliation: Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hofmann-Winkler
authors.affiliation: Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.|Institut für Mikrobiologie und Virologie, Medizinische Hochschule Brandenburg Theodor Fontane, Senftenberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Spiegel
authors.affiliation: Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0001-6086-9136
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D010217:Phlebotomus Fever / Q000821:virology*; D016856:Phlebovirus / Q000472:pathogenicity / Q000502:physiology*; D020815:Polyproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport; D059748:Proteolysis; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D053586:Virus Internalization
chemical_list: D006023:Glycoproteins; D020815:Polyproteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins