2026-04-23T05:56:01Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/109242025-10-07T10:26:06Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Aydillo, Teresa 8f82dd28-7cef-4f5a-9272-5b6fa9eae736 600 Ayllón Barasoain, Juan 852 600 0000-0002-7556-8106 Pavlisin, Amzie 67d55203-72c3-48bc-b0ec-a51a6024707b 500 Martinez-Romero, Carles efe96be2-554a-49a9-92ed-f0edbeb5350e 500 Tripathi, Shashank 396741e8-ac23-4660-a600-79f4a3e22582 500 Mena, Ignacio 5f7d032e-0d94-44b4-bb61-8f941c15b59e 500 Moreira-Soto, Andrés 37c4f92e-21e0-4a6b-9837-dd4d736a6e0c 500 Vicente-Santos, Amanda ee9491ea-c6f6-4df7-b44f-e85a36ea98dc 500 Corrales-Aguilar, Eugenia 8a4ddc87-2a94-4851-972e-b6a4fd8f04e9 500 Schwemmle, Martin 296f2d38-6205-4cb2-85c7-6cceb0accb8b 500 García Sastre, Adolfo 9de2ea8b-c019-414d-bb90-b1d51ef5bbd7 600 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. We thank Megan Shaw for the firefly luciferase-expressing viral minigenome construct pPoI-FFLuc-RT and Peter Palese for the anti-NS1-155 antibody. We also thank Jaime Tome for technical assistance. Microscopy was performed at the Microscopy CoRE at the Icahn School of Medicine at Mount Sinai. The study was supported by the Center for Research on Influenza Pathogenesis (CRIP), an NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS contract number HHSN272201400008C to A.G.-S), by the Deutsche Forschungsgemeinschaft (SCHW632/15-1 to M.S.), and by FEES-CONARE VI-803-B4-656 and the European Union's Horizon 2020 to E.C.-A. (ZIKAlliance grant agreement no. 734548). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. application/pdf eng American Society for Microbiology Journal of Virology. 2018, V. 14, n. 92, e02021-17 https://doi.org/10.1128/jvi.02021-17 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Influenza viruses NS1 protein Bat Interferons Proteínas Proteins 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 info:eu-repo/semantics/acceptedVersion Journal of Virology 92 7 THUMBNAIL Aydillo-jv _2018.pdf.jpg Aydillo-jv _2018.pdf.jpg IM Thumbnail image/jpeg 4386 https://riubu.ubu.es/bitstream/10259/10924/4/Aydillo-jv%20_2018.pdf.jpg edf4ac63147ff6f81cd2e3d06656be12 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/10924/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/10924/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Aydillo-jv _2018.pdf Aydillo-jv _2018.pdf application/pdf 1794353 https://riubu.ubu.es/bitstream/10259/10924/1/Aydillo-jv%20_2018.pdf ce05ed7680d335691935b8b61f5c6b16 MD5 1 10259/10924 oai:riubu.ubu.es:10259/10924 2025-10-07 12:26:06.637 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es RWwgYXV0b3IgY29tbyDDum5pY28gdGl0dWxhciBkZSBsb3MgZGVyZWNob3MgZGUgcHJvcGllZGFkIGludGVsZWN0dWFsIGRlIGxhIG9icmEsIG8gZGlzcG9uaWVuZG8gZGUgbG9zIGRlYmlkb3MgcGVybWlzb3MgZGUgbG9zIG90cm9zIHRpdHVsYXJlcywgc2kgbG9zIGh1YmllcmEsIHkgZW4gdmlydHVkIGRlIGxvcyBkZXJlY2hvcyBxdWUgbGUgY29uZmllcmUgbGEgbGVnaXNsYWNpw7NuIHZpZ2VudGUgc29icmUgcHJvcGllZGFkIGludGVsZWN0dWFsIHkgZGVyZWNob3MgZGUgYXV0b3IsIA0KQVVUT1JJWkEgYSBsYSBVbml2ZXJzaWRhZCBkZSBCdXJnb3MgYSBkaWZ1bmRpciwgZGUgbWFuZXJhIGdyYXR1aXRhLCBlbCBjb250ZW5pZG8gZGUgbG9zIGFyY2hpdm9zIGRpZ2l0YWxlcyBxdWUgY29ycmVzcG9uZGVuIGFsIGRvY3VtZW50byBkZXNjcml0byBhbnRlcmlvcm1lbnRlLCBjb24gY2Fyw6FjdGVyIG5vIGV4Y2x1c2l2byB5IGRlIG1hbmVyYSBww7pibGljYSBlbiBhY2Nlc28gYWJpZXJ0byBhIHRyYXbDqXMgZGUgSW50ZXJuZXQsIHBhcmEgbG8gcXVlIGxhIEJpYmxpb3RlY2EgcHJvY2VkZXLDoSBhIGFyY2hpdmFybG9zIGVuIGVsIFJlcG9zaXRvcmlvIEluc3RpdHVjaW9uYWwuIEFzaW1pc21vIGF1dG9yaXphIGEgbGEgVW5pdmVyc2lkYWQgZGUgQnVyZ29zIGEgcmVhbGl6YXIgbGFzIHRyYW5zZm9ybWFjaW9uZXMgbmVjZXNhcmlhcyBkZSBmb3JtYXRvLCBubyBkZSBjb250ZW5pZG8sIHBhcmEgZ2FyYW50aXphciBsYSBwcmVzZXJ2YWNpw7NuIHkgZWwgYWNjZXNvIGVuIGVsIGZ1dHVyby4NCg0KRWwgYXV0b3IgZGlzcG9uZSwgZW4gdG9kbyBjYXNvLCBkZWwgZGVyZWNobyBhIHJldm9jYXIgZXN0YSBhdXRvcml6YWNpw7NuLg0KDQpMYSBjZXNpw7NuIGRlIGRlcmVjaG9zIGRlIGVzdGEgb2JyYSBzZSBlbmN1ZW50cmEgc3VqZXRhIGEgbGEgbGVnaXNsYWNpw7NuIHZpZ2VudGUgc29icmUgcHJvcGllZGFkIGludGVsZWN0dWFsIHkgZGVyZWNob3MgZGUgYXV0b3Iu