Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background.

2.50
Hdl Handle:
http://hdl.handle.net/10033/615960
Title:
Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background.
Authors:
Shin, Dai-Lun; Hatesuer, Bastian; Bergmann, Silke; Nedelko, Tatiana; Schughart, Klaus ( 0000-0002-6824-7523 )
Abstract:
Influenza virus infections represent a serious threat to human health. Both extrinsic and intrinsic factors determine the severity of influenza. The MX dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to influenza A virus infections in mice. Most laboratory mouse strains, including C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic C57BL/6J (B6-Mx1(r/r)) mice expressing a wild-type allele from the A2G mouse strain are highly resistant to influenza A virus infections, to both mono- and polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified as the major locus of resistance to influenza virus infections. Here, we investigated whether the Mx1 protective function is influenced by the genetic background. For this, we generated a congenic mouse strain carrying the A2G wild-type Mx1 resistance allele on a DBA/2J background (D2-Mx1(r/r)). Most remarkably, congenic D2-Mx1(r/r) mice expressing a functional Mx1 wild-type allele are still highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1(r/r) mice with alpha interferon protected them from lethal infections. Our results showed, for the first time, that the presence of an Mx1 wild-type allele from A2G as such does not fully protect mice from lethal influenza A virus infections. These observations are also highly relevant for susceptibility to influenza virus infections in humans.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background. 2015, 89 (19):9998-10009 J. Virol.
Journal:
Journal of virology
Issue Date:
Oct-2015
URI:
http://hdl.handle.net/10033/615960
DOI:
10.1128/JVI.01305-15
PubMed ID:
26202236
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorShin, Dai-Lunen
dc.contributor.authorHatesuer, Bastianen
dc.contributor.authorBergmann, Silkeen
dc.contributor.authorNedelko, Tatianaen
dc.contributor.authorSchughart, Klausen
dc.date.accessioned2016-07-12T10:37:52Z-
dc.date.available2016-07-12T10:37:52Z-
dc.date.issued2015-10-
dc.identifier.citationProtection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background. 2015, 89 (19):9998-10009 J. Virol.en
dc.identifier.issn1098-5514-
dc.identifier.pmid26202236-
dc.identifier.doi10.1128/JVI.01305-15-
dc.identifier.urihttp://hdl.handle.net/10033/615960-
dc.description.abstractInfluenza virus infections represent a serious threat to human health. Both extrinsic and intrinsic factors determine the severity of influenza. The MX dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to influenza A virus infections in mice. Most laboratory mouse strains, including C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic C57BL/6J (B6-Mx1(r/r)) mice expressing a wild-type allele from the A2G mouse strain are highly resistant to influenza A virus infections, to both mono- and polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified as the major locus of resistance to influenza virus infections. Here, we investigated whether the Mx1 protective function is influenced by the genetic background. For this, we generated a congenic mouse strain carrying the A2G wild-type Mx1 resistance allele on a DBA/2J background (D2-Mx1(r/r)). Most remarkably, congenic D2-Mx1(r/r) mice expressing a functional Mx1 wild-type allele are still highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1(r/r) mice with alpha interferon protected them from lethal infections. Our results showed, for the first time, that the presence of an Mx1 wild-type allele from A2G as such does not fully protect mice from lethal influenza A virus infections. These observations are also highly relevant for susceptibility to influenza virus infections in humans.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshBronchoalveolar Lavage Fluiden
dc.subject.meshCytokinesen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHost Specificityen
dc.subject.meshHumansen
dc.subject.meshInfluenza A Virus, H1N1 Subtypeen
dc.subject.meshInfluenza A Virus, H3N2 Subtypeen
dc.subject.meshInfluenza, Humanen
dc.subject.meshInterferon-alphaen
dc.subject.meshMiceen
dc.subject.meshMice, Congenicen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Inbred DBAen
dc.subject.meshMice, Knockouten
dc.subject.meshMutationen
dc.subject.meshMyxovirus Resistance Proteinsen
dc.subject.meshOrthomyxoviridae Infectionsen
dc.subject.meshVirus Replicationen
dc.titleProtection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalJournal of virologyen

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