Open AccessSubstitutions 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
Author(s) -
Magali E. Droniou-Bonzom,
Therese Reignier,
Jill Oldenburg,
Alex U. Cox,
Colin M. Exline,
Jessica Y. Rathbun,
Paula M. Can
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.05616-11
Subject(s) - junin virus , biology , virology , tropism , glycoprotein , infectivity , transmembrane protein , transferrin receptor , virus , phenotype , viral entry , protein subunit , strain (injury) , receptor , viral replication , genetics , in vitro , gene , lymphocytic choriomeningitis , cytotoxic t cell , anatomy
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 strainin vivo .