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Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein
The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strai...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114831/ https://www.ncbi.nlm.nih.gov/pubmed/29936068 http://dx.doi.org/10.1016/j.virusres.2018.06.010 |
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author | Shirato, Kazuya Chang, Hui-Wen Rottier, Peter J.M. |
author_facet | Shirato, Kazuya Chang, Hui-Wen Rottier, Peter J.M. |
author_sort | Shirato, Kazuya |
collection | PubMed |
description | The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). In view of the later identified diagnostic difference in this very part of the S protein of serotype I FCoV pathotypes, the present study aimed to further define the contribution of the earlier observed ten amino acids difference to the serotype II virus phenotype in macrophages. Using targeted RNA recombination as a reverse genetics system we introduced the mutations singly and in combinations into the S gene and evaluated their effects on the infection characteristics of the mutant viruses in macrophages. While some of the single mutations had a significant effect, none of them fully reverted the infection phenotype. Only by combining five specific mutations the infections mediated by the FIPV and FECV spike proteins could be fully blocked or potentiated, respectively. Hence, the differential macrophage infection phenotype is caused by the cooperative effect of five mutations, which occur in five functionally different domains of the spike fusion subunit S2. The significance of these observations will be discussed, taking into account also some questions related to the identity of the virus strains used. |
format | Online Article Text |
id | pubmed-7114831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71148312020-04-02 Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein Shirato, Kazuya Chang, Hui-Wen Rottier, Peter J.M. Virus Res Article The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). In view of the later identified diagnostic difference in this very part of the S protein of serotype I FCoV pathotypes, the present study aimed to further define the contribution of the earlier observed ten amino acids difference to the serotype II virus phenotype in macrophages. Using targeted RNA recombination as a reverse genetics system we introduced the mutations singly and in combinations into the S gene and evaluated their effects on the infection characteristics of the mutant viruses in macrophages. While some of the single mutations had a significant effect, none of them fully reverted the infection phenotype. Only by combining five specific mutations the infections mediated by the FIPV and FECV spike proteins could be fully blocked or potentiated, respectively. Hence, the differential macrophage infection phenotype is caused by the cooperative effect of five mutations, which occur in five functionally different domains of the spike fusion subunit S2. The significance of these observations will be discussed, taking into account also some questions related to the identity of the virus strains used. Elsevier B.V. 2018-08-15 2018-06-21 /pmc/articles/PMC7114831/ /pubmed/29936068 http://dx.doi.org/10.1016/j.virusres.2018.06.010 Text en © 2018 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Shirato, Kazuya Chang, Hui-Wen Rottier, Peter J.M. Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title | Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title_full | Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title_fullStr | Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title_full_unstemmed | Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title_short | Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein |
title_sort | differential susceptibility of macrophages to serotype ii feline coronaviruses correlates with differences in the viral spike protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114831/ https://www.ncbi.nlm.nih.gov/pubmed/29936068 http://dx.doi.org/10.1016/j.virusres.2018.06.010 |
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