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Machmouchi, Dana, Courageot, Marie-Pierre, Ogire, Eva, Redecke, Lars, Kohl, Alain, Desprès, Philippe and Roche, Marjolaine (2024) 'The NS1 protein of contemporary West African Zika virus potentiates viral replication and reduces innate immune activation.'. PLoS Neglected Tropical Diseases, Vol 18, Issue 8, e0012146.
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Abstract
Mosquito-borne Zika virus (ZIKV) from sub-Saharan Africa has recently gained attention due to its epidemic potential and its capacity to be highly teratogenic. To improve our knowledge on currently circulating strains of African ZIKV, we conducted protein sequence alignment and identified contemporary West Africa NS1 (NS1CWA) protein as a highly conserved viral protein. Comparison of NS1CWA with the NS1 of the historical African ZIKV strain MR766 (NS1MR766), revealed seven amino acid substitutions. The effects of NS1 mutations on protein expression, virus replication, and innate immune activation were assessed in human cells using recombinant NS1 proteins and a chimeric viral clone MR766 with NS1CWA replacing NS1MR766. Our data indicated higher secretion efficiency of NS1CWA compared to NS1MR766 associated with a change in subcellular distribution. A chimeric MR766 virus with NS1CWA instead of authentic protein displayed a greater viral replication efficiency, leading to more pronounced cell death compared to parental virus. Enhanced viral growth was associated with reduced activation of innate immunity. Our data raise questions of the importance of NS1 protein in the pathogenicity of contemporary ZIKV from sub-Saharan Africa and point to differences within viral strains of African lineage.
| Item Type: | Article |
|---|---|
| Subjects: | QW Microbiology and Immunology > Viruses > QW 162 Insect viruses QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1371/journal.pntd.0012146 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 23 Sep 2024 13:38 |
| Last Modified: | 23 Sep 2024 13:38 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25275 |
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