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Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein
Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide, that possesses both enteric and respiratory tropism. The ability to replicate in the enteric tract directly correlates with virulence, as TGEVs with an exclusive resp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168613/ https://www.ncbi.nlm.nih.gov/pubmed/31861369 http://dx.doi.org/10.3390/pathogens9010002 |
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author | Sanchez, Carlos M. Pascual-Iglesias, Alejandro Sola, Isabel Zuñiga, Sonia Enjuanes, Luis |
author_facet | Sanchez, Carlos M. Pascual-Iglesias, Alejandro Sola, Isabel Zuñiga, Sonia Enjuanes, Luis |
author_sort | Sanchez, Carlos M. |
collection | PubMed |
description | Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide, that possesses both enteric and respiratory tropism. The ability to replicate in the enteric tract directly correlates with virulence, as TGEVs with an exclusive respiratory tropism are attenuated. The tissue tropism is determined by spike (S) protein, although the molecular bases for enteric tropism remain to be fully characterized. Both pAPN and sialic acid binding domains (aa 506–655 and 145–155, respectively) are necessary but not sufficient for enteric tract infection. Using a TGEV infectious cDNA and enteric (TGEV-SC11) or respiratory (TGEV-SPTV) isolates, encoding a full-length S protein, a set of chimeric recombinant viruses, with a sequential modification in S protein amino terminus, was engineered. In vivo tropism, either enteric, respiratory or both, was studied by inoculating three-day-old piglets and analyzing viral titers in lung and gut. The data indicated that U655>G change in S gene (S219A in S protein) was required to confer enteric tropism to a respiratory virus that already contains the pAPN and sialic acid binding domains in its S protein. Moreover, an engineered virus containing U655>G and a 6 nt insertion at position 1124 (Y374-T375insND in S protein) was genetically stable after passage in cell cultures, and increased virus titers in gut by 1000-fold. We postulated that the effect of these residues in enteric tropism may be mediated by the modification of both glycosaminoglycan binding and S protein structure. |
format | Online Article Text |
id | pubmed-7168613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71686132020-04-22 Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein Sanchez, Carlos M. Pascual-Iglesias, Alejandro Sola, Isabel Zuñiga, Sonia Enjuanes, Luis Pathogens Article Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide, that possesses both enteric and respiratory tropism. The ability to replicate in the enteric tract directly correlates with virulence, as TGEVs with an exclusive respiratory tropism are attenuated. The tissue tropism is determined by spike (S) protein, although the molecular bases for enteric tropism remain to be fully characterized. Both pAPN and sialic acid binding domains (aa 506–655 and 145–155, respectively) are necessary but not sufficient for enteric tract infection. Using a TGEV infectious cDNA and enteric (TGEV-SC11) or respiratory (TGEV-SPTV) isolates, encoding a full-length S protein, a set of chimeric recombinant viruses, with a sequential modification in S protein amino terminus, was engineered. In vivo tropism, either enteric, respiratory or both, was studied by inoculating three-day-old piglets and analyzing viral titers in lung and gut. The data indicated that U655>G change in S gene (S219A in S protein) was required to confer enteric tropism to a respiratory virus that already contains the pAPN and sialic acid binding domains in its S protein. Moreover, an engineered virus containing U655>G and a 6 nt insertion at position 1124 (Y374-T375insND in S protein) was genetically stable after passage in cell cultures, and increased virus titers in gut by 1000-fold. We postulated that the effect of these residues in enteric tropism may be mediated by the modification of both glycosaminoglycan binding and S protein structure. MDPI 2019-12-18 /pmc/articles/PMC7168613/ /pubmed/31861369 http://dx.doi.org/10.3390/pathogens9010002 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sanchez, Carlos M. Pascual-Iglesias, Alejandro Sola, Isabel Zuñiga, Sonia Enjuanes, Luis Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title | Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title_full | Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title_fullStr | Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title_full_unstemmed | Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title_short | Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein |
title_sort | minimum determinants of transmissible gastroenteritis virus enteric tropism are located in the n-terminus of spike protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168613/ https://www.ncbi.nlm.nih.gov/pubmed/31861369 http://dx.doi.org/10.3390/pathogens9010002 |
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