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Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism
The β-Coronavirus mouse hepatitis virus (MHV-A59)-RSA59 has a patent stretch of fusion peptide (FP) containing two consecutive central prolines (PP) in the S2 domain of the Spike protein. Our previous studies compared the PP-containing fusogenic-demyelinating strain RSA59(PP) to its one proline-dele...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865228/ https://www.ncbi.nlm.nih.gov/pubmed/36680255 http://dx.doi.org/10.3390/v15010215 |
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author | Safiriyu, Abass Alao Mulchandani, Vaishali Anakkacheri, Mohammed Nahaf Pal, Debnath Das Sarma, Jayasri |
author_facet | Safiriyu, Abass Alao Mulchandani, Vaishali Anakkacheri, Mohammed Nahaf Pal, Debnath Das Sarma, Jayasri |
author_sort | Safiriyu, Abass Alao |
collection | PubMed |
description | The β-Coronavirus mouse hepatitis virus (MHV-A59)-RSA59 has a patent stretch of fusion peptide (FP) containing two consecutive central prolines (PP) in the S2 domain of the Spike protein. Our previous studies compared the PP-containing fusogenic-demyelinating strain RSA59(PP) to its one proline-deleted mutant strain RSA59(P) and one proline-containing non-fusogenic non-demyelinating parental strain RSMHV2(P) to its one proline inserted mutant strain RSMHV2(PP). These studies highlighted the crucial role of PP in fusogenicity, hepato-neuropathogenesis, and demyelination. Computational studies combined with biophysical data indicate that PP at the center of the FP provides local rigidity while imparting global fluctuation to the Spike protein that enhances the fusogenic properties of RSA59(PP) and RSMHV2(PP). To elaborate on the understanding of the role of PP in the FP of MHV, the differential neuroglial tropism of the PP and P mutant strains was investigated. Comparative studies demonstrated that PP significantly enhances the viral tropism for neurons, microglia, and oligodendrocytes. PP, however, is not essential for viral tropism for either astroglial or oligodendroglial precursors or the infection of meningeal fibroblasts in the blood–brain and blood–CSF barriers. PP in the fusion domain is critical for promoting gliopathy, making it a potential region for designing antivirals for neuro-COVID therapy. |
format | Online Article Text |
id | pubmed-9865228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98652282023-01-22 Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism Safiriyu, Abass Alao Mulchandani, Vaishali Anakkacheri, Mohammed Nahaf Pal, Debnath Das Sarma, Jayasri Viruses Article The β-Coronavirus mouse hepatitis virus (MHV-A59)-RSA59 has a patent stretch of fusion peptide (FP) containing two consecutive central prolines (PP) in the S2 domain of the Spike protein. Our previous studies compared the PP-containing fusogenic-demyelinating strain RSA59(PP) to its one proline-deleted mutant strain RSA59(P) and one proline-containing non-fusogenic non-demyelinating parental strain RSMHV2(P) to its one proline inserted mutant strain RSMHV2(PP). These studies highlighted the crucial role of PP in fusogenicity, hepato-neuropathogenesis, and demyelination. Computational studies combined with biophysical data indicate that PP at the center of the FP provides local rigidity while imparting global fluctuation to the Spike protein that enhances the fusogenic properties of RSA59(PP) and RSMHV2(PP). To elaborate on the understanding of the role of PP in the FP of MHV, the differential neuroglial tropism of the PP and P mutant strains was investigated. Comparative studies demonstrated that PP significantly enhances the viral tropism for neurons, microglia, and oligodendrocytes. PP, however, is not essential for viral tropism for either astroglial or oligodendroglial precursors or the infection of meningeal fibroblasts in the blood–brain and blood–CSF barriers. PP in the fusion domain is critical for promoting gliopathy, making it a potential region for designing antivirals for neuro-COVID therapy. MDPI 2023-01-12 /pmc/articles/PMC9865228/ /pubmed/36680255 http://dx.doi.org/10.3390/v15010215 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Safiriyu, Abass Alao Mulchandani, Vaishali Anakkacheri, Mohammed Nahaf Pal, Debnath Das Sarma, Jayasri Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title | Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title_full | Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title_fullStr | Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title_full_unstemmed | Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title_short | Proline–Proline Dyad in the Fusion Peptide of the Murine β–Coronavirus Spike Protein’s S2 Domain Modulates Its Neuroglial Tropism |
title_sort | proline–proline dyad in the fusion peptide of the murine β–coronavirus spike protein’s s2 domain modulates its neuroglial tropism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865228/ https://www.ncbi.nlm.nih.gov/pubmed/36680255 http://dx.doi.org/10.3390/v15010215 |
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