2026-04-29T10:54:05Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/109242025-10-07T10:26:06Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863
Repositorio Institucional de la Universidad de Burgos
author
Aydillo, Teresa
author
Ayllón Barasoain, Juan
author
Pavlisin, Amzie
author
Martinez-Romero, Carles
author
Tripathi, Shashank
author
Mena, Ignacio
author
Moreira-Soto, Andrés
author
Vicente-Santos, Amanda
author
Corrales-Aguilar, Eugenia
author
Schwemmle, Martin
author
García Sastre, Adolfo
2025-10-06T09:17:52Z
2025-10-06T09:17:52Z
2018-03
0022-538X
https://hdl.handle.net/10259/10924
10.1128/JVI.02021-17
1098-5514
Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo. However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1−/− human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein.
eng
Atribución 4.0 Internacional
Influenza viruses
NS1 protein
Bat
Interferons
Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses
info:eu-repo/semantics/article
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https://riubu.ubu.es/bitstream/10259/10924/1/Aydillo-jv%20_2018.pdf
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Aydillo-jv _2018.pdf