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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution
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Animals
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Antigens, CD / metabolism*
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Cell Line
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Humans
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Junin virus / genetics
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Junin virus / pathogenicity*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Protein Conformation
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Receptors, Transferrin / metabolism*
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Receptors, Virus / metabolism*
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Vaccines, Attenuated / genetics
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Viral Envelope Proteins / chemistry
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism*
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Viral Vaccines / genetics
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Virulence Factors / chemistry
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Virulence Factors / genetics
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Virulence Factors / metabolism*
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Virus Internalization*
Substances
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Antigens, CD
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CD71 antigen
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Membrane Glycoproteins
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Receptors, Transferrin
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Receptors, Virus
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Vaccines, Attenuated
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Viral Envelope Proteins
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Viral Vaccines
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Virulence Factors