title: Substitutions in the glycoprotein (GP) of the Candid#1 vaccine strain of Junin virus increase dependence on human transferrin receptor 1 for entry and destabilize the metastable conformation of GP.
abstract: Candid#1 (Cd1) is an attenuated vaccine strain of Junin virus, the causative agent of Argentine hemorrhagic fever. Although several substitutions are present in Cd1, their importance for attenuation has not been established. We functionally characterized the substitutions present in the Cd1 glycoprotein (GP) and identified F427I in the transmembrane domain of the GP2 subunit as reducing infectivity in a reconstituted viral system. We further showed that this phenotype derives from the destabilization of the GP metastable conformation. Lastly, we identified an increased dependence of Cd1 GP on human transferrin receptor type 1 (hTfR-1) for entry, which may affect the tropism of the attenuated strain in vivo.
authors: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR502, Los Angeles, CA 90033, USA.
authors: Magali E
authors: ME
authors: Droniou-Bonzom
authors: Therese
authors: T
authors: Reignier
authors: Jill E
authors: JE
authors: Oldenburg
authors: Alex U
authors: AU
authors: Cox
authors: Colin M
authors: CM
authors: Exline
authors: Jessica Y
authors: JY
authors: Rathbun
authors: Paula M
authors: PM
authors: Cannon
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D018051:Junin virus / Q000235:genetics / Q000472:pathogenicity*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011990:Receptors, Transferrin / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014613:Vaccines, Attenuated / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014765:Viral Vaccines / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D008562:Membrane Glycoproteins; D011990:Receptors, Transferrin; D011991:Receptors, Virus; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D037521:Virulence Factors