1887

Abstract

Lassa virus glycoprotein 2 (LASV GP-2) belongs to the class I fusion protein family. Its N terminus contains two stretches of highly conserved hydrophobic amino acids (residues 260–266 and 276–298) that have been proposed as N-terminal or internal fusion peptide segments (N-FPS, I-FPS) by analogy with similar sequences of other viral glycoproteins or based on experimental data obtained with synthetic peptides, respectively. By using a pH-dependent, recombinant LASV glycoprotein mediated cell–cell fusion assay and a retroviral pseudotype infectivity assay, an alanine scan of all hydrophobic amino acids within both proposed FPSs was performed. Fusogenicity and infectivity were correlated, both requiring correct processing of the glycoprotein precursor. Most point mutations in either FPS accounted for reduced or abolished fusion or infection, respectively. Some mutations also had an effect on pre-fusion steps of virus entry, possibly by inducing structural changes in the glycoprotein. The data demonstrate that several amino acids from both hydrophobic regions of the N terminus, some of which (W264, G277, Y278 and L280) are 100 % conserved in all arenaviruses, are involved in fusogenicity and infectivity of LASV GP-2.

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2007-08-01
2020-01-20
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