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Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections

The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influenc...

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Autores principales: Srivastava, Barkha, Błażejewska, Paulina, Heßmann, Manuela, Bruder, Dunja, Geffers, Robert, Mauel, Susanne, Gruber, Achim D., Schughart, Klaus
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654507/
https://www.ncbi.nlm.nih.gov/pubmed/19293935
http://dx.doi.org/10.1371/journal.pone.0004857
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author Srivastava, Barkha
Błażejewska, Paulina
Heßmann, Manuela
Bruder, Dunja
Geffers, Robert
Mauel, Susanne
Gruber, Achim D.
Schughart, Klaus
author_facet Srivastava, Barkha
Błażejewska, Paulina
Heßmann, Manuela
Bruder, Dunja
Geffers, Robert
Mauel, Susanne
Gruber, Achim D.
Schughart, Klaus
author_sort Srivastava, Barkha
collection PubMed
description The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD(50) to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses.
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spelling pubmed-26545072009-03-18 Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections Srivastava, Barkha Błażejewska, Paulina Heßmann, Manuela Bruder, Dunja Geffers, Robert Mauel, Susanne Gruber, Achim D. Schughart, Klaus PLoS One Research Article The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD(50) to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses. Public Library of Science 2009-03-18 /pmc/articles/PMC2654507/ /pubmed/19293935 http://dx.doi.org/10.1371/journal.pone.0004857 Text en Srivastava et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Srivastava, Barkha
Błażejewska, Paulina
Heßmann, Manuela
Bruder, Dunja
Geffers, Robert
Mauel, Susanne
Gruber, Achim D.
Schughart, Klaus
Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title_full Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title_fullStr Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title_full_unstemmed Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title_short Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections
title_sort host genetic background strongly influences the response to influenza a virus infections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654507/
https://www.ncbi.nlm.nih.gov/pubmed/19293935
http://dx.doi.org/10.1371/journal.pone.0004857
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