title: Characterization of the Bas-Congo virus glycoprotein and its function in pseudotyped viruses.
abstract: Bas-Congo virus (BASV) is a novel rhabdovirus recently identified from a patient with acute hemorrhagic fever in the Bas-Congo province of the Democratic Republic of Congo (DRC). Here we show that the BASV glycoprotein (BASV-G) can be successfully used to pseudotype glycoprotein-deficient vesicular stomatitis virus (VSV), allowing studies of BASV-G-driven membrane fusion and viral entry into target cells without replication-competent virus. BASV-G displayed broad tissue and species tropism in vitro, and BASV-G-mediated membrane fusion was pH dependent. The conformational changes induced in BASV-G by acidification were fully reversible and did not lead to inactivation of the viral fusion protein. Our data combined with comparative sequence similarity analyses suggest that BASV-G shares structural and functional features with other rhabdovirus glycoproteins and falls into the group of class III viral fusion proteins. However, activation of BASV-G-driven fusion required a lower pH and higher temperatures than did VSV-G-mediated fusion. Moreover, in contrast to VSV-G, mature BASV-G in VSV pseudotypes consists of a mixture of high-mannose and complex glycans that enables it to bind to certain C-type lectins, thereby enhancing its attachment to target cells. Taken together, the results presented in this study will facilitate future investigations of BASV-G-mediated cell entry and its inhibition in the absence of an infectious cell culture assay for BASV and at lower biosafety levels. Moreover, serology testing based on BASV-G pseudotype neutralization can be used to uncover the prevalence and importance of BASV as a potential novel human pathogen in the DRC and throughout Central Africa.
authors.affiliation: Blood Systems Research Institute, San Francisco, California, USA.
authors.forename: Imke
authors.initials: I
authors.lastname: Steffen
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Liss
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Schneider
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Fair
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Chiu
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003223:Congo; D006224:Cricetinae; D006801:Humans; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D012209:Rhabdoviridae / Q000145:classification / Q000235:genetics / Q000502:physiology*; D018353:Rhabdoviridae Infections / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D053586:Virus Internalization
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins