Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR502, Los Angeles, CA 90033, USA.
J Virol. 2011 Dec;85(24):13457-62. doi: 10.1128/JVI.05616-11. Epub 2011 Oct 5.
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.
Candid#1（Cd1）是一种减毒的胡宁病毒株，胡宁病毒是阿根廷出血热的病原体。尽管 Cd1 中有几个取代，但它们对减毒的重要性尚未确定。我们对 Cd1 糖蛋白（GP）中的取代进行了功能表征，并确定了 GP2 亚基跨膜结构域中的 F427I 降低了重建病毒系统中的感染性。我们进一步表明，这种表型源自 GP 亚稳定构象的不稳定性。最后，我们发现 Cd1 GP 对人转铁蛋白受体 1（hTfR-1）的依赖性增加，这可能影响减毒菌株在体内的趋向性。
