Instability of the NS1 Glycoprotein from La Reunion 2018 Dengue 2 Virus (Cosmopolitan-1 Genotype) in Huh7 Cells Is Due to Lysine Residues on Positions 272 and 324 |
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Authors: | Eva Ogire Olivier Diaz Pierre-Olivier Vidalain Vincent Lotteau Philippe Desprs Marjolaine Roche |
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Affiliation: | 1.Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion, Inserm UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, France;2.Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Ecole Normale Supérieure de Lyon, Inserm, U1111, CNRS, UMR5308, 69007 Lyon, France; (O.D.); (P.-O.V.); (V.L.) |
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Abstract: | La Reunion island in the South West Indian Ocean is now endemic for dengue following the introduction of dengue virus serotype 2 (DENV-2) cosmopolitan-I genotype in 2017. DENV-2 infection causes a wide spectrum of clinical manifestations ranging from flu-like disease to severe dengue. The nonstructural glycoprotein 1 (NS1) has been identified as playing a key role in dengue disease severity. The intracellular NS1 exists as a homodimer, whereas a fraction is driven towards the plasma membrane or released as a soluble hexameric protein. Here, we characterized the NS1 glycoproteins from clinical isolates DES-14 and RUN-18 that were collected during the DENV-2 epidemics in Tanzania in 2014 and La Reunion island in 2018, respectively. In relation to hepatotropism of the DENV, expression of recombinant DES-14 NS1 and RUN-18 NS1 glycoproteins was compared in human hepatoma Huh7 cells. We observed that RUN-18 NS1 was poorly stable in Huh7 cells compared to DES-14 NS1. The instability of RUN-18 NS1 leading to a low level of NS1 secretion mostly relates to lysine residues on positions 272 and 324. Our data raise the issue of the consequences of a defect in NS1 stability in human hepatocytes in relation to the major role of NS1 in the pathogenesis of the DENV-2 infection. |
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Keywords: | arbovirus flavivirus dengue virus nonstructural protein 1 soluble viral protein multimeric viral protein recombinant viral protein hepatoma cells |
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