Limits...
Host genetic background strongly influences the response to influenza a virus infections.

Srivastava B, Błazejewska P, Hessmann M, Bruder D, Geffers R, Mauel S, Gruber AD, Schughart K - PLoS ONE (2009)

Bottom Line: The genetic make-up of the host has a major influence on its response to combat pathogens.Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains.These findings indicate a major contribution of the genetic background of the host to influenza A virus infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Mouse Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Germany.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Severe damage of bronchial epithelia occurs in DBA/2J compared to C57BL/6J mice.DBA/2J (A, C, E) and C57BL/6J mice (B, D, F) were infected intra-nasally with 2×103 FFU of PR8 virus. Lung sections were stained with hematoxylin and eosin. A, B: Two days after infection, the lungs of DBA/2J mice (A) were more consolidated with higher numbers of plugged airways (arrows) than C57BL/6J mice (B). C, D: The bronchioli and bronchi of DBA/2J mice (C) were plugged with degenerate bronchial epithelial cells and neutrophils with higher degrees of degeneration, necrosis and loss of epithelial cells (arrows) two days after infection. In addition, the airways were surrounded by larger numbers of neutrophils and macrophages (asterisks). Airways of C57BL/6J mice (D) showed less damage with little or no plugging of airways. At that time point, the lungs of both strains had few infiltrations with lymphocytes. E, F: Four days after infection, virtually no extravasations of lymphocytes were detected in DBA/2J mice (E) whereas marked perivascular lymphocytic infiltrations (arrows) were observed in the pulmonary interstitium of C57BL/6J mice (F). Bars  =  250 µm (A, B), 25 µm (C, D) and 50 µm (E, F).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654507&req=5

pone-0004857-g008: Severe damage of bronchial epithelia occurs in DBA/2J compared to C57BL/6J mice.DBA/2J (A, C, E) and C57BL/6J mice (B, D, F) were infected intra-nasally with 2×103 FFU of PR8 virus. Lung sections were stained with hematoxylin and eosin. A, B: Two days after infection, the lungs of DBA/2J mice (A) were more consolidated with higher numbers of plugged airways (arrows) than C57BL/6J mice (B). C, D: The bronchioli and bronchi of DBA/2J mice (C) were plugged with degenerate bronchial epithelial cells and neutrophils with higher degrees of degeneration, necrosis and loss of epithelial cells (arrows) two days after infection. In addition, the airways were surrounded by larger numbers of neutrophils and macrophages (asterisks). Airways of C57BL/6J mice (D) showed less damage with little or no plugging of airways. At that time point, the lungs of both strains had few infiltrations with lymphocytes. E, F: Four days after infection, virtually no extravasations of lymphocytes were detected in DBA/2J mice (E) whereas marked perivascular lymphocytic infiltrations (arrows) were observed in the pulmonary interstitium of C57BL/6J mice (F). Bars  =  250 µm (A, B), 25 µm (C, D) and 50 µm (E, F).

Mentions: Histological analyses of infected mice revealed striking differences between the tissue lesions in DBA/2J and C57BL/6J mice. The overall lung tissues were more densely consolidated with larger numbers of affected airways in DBA/2J mice compared to C57BL/6J mice (figure 8A, B). In both mouse strains, bronchial and bronchiolar epithelial cells showed degeneration, necrosis and loss with accumulation of sloughed cells and mostly degenerate neutrophils in the airway lumen at days 2 and 3 after infection. However, the degree of bronchial epithelial necrosis and airway plugging by cellular debris was much more pronounced in DBA/2J than C57BL/6J mice. This was accompanied by larger numbers of neutrophils and macrophages around the affected airways in DBA/2J mice (figure 8C, D). On the other hand, C57BL/6J mice developed a much stronger perivascular and peribronchial infiltration of lymphocytes at day 4 after infection (figure 8E, F). Alveolar epithelial cells were mostly unaffected. Few macrophages and virtually no plasma cells were seen in the lungs, with no differences between the two mouse strains at days 2 to 4 post infection.


Host genetic background strongly influences the response to influenza a virus infections.

Srivastava B, Błazejewska P, Hessmann M, Bruder D, Geffers R, Mauel S, Gruber AD, Schughart K - PLoS ONE (2009)

Severe damage of bronchial epithelia occurs in DBA/2J compared to C57BL/6J mice.DBA/2J (A, C, E) and C57BL/6J mice (B, D, F) were infected intra-nasally with 2×103 FFU of PR8 virus. Lung sections were stained with hematoxylin and eosin. A, B: Two days after infection, the lungs of DBA/2J mice (A) were more consolidated with higher numbers of plugged airways (arrows) than C57BL/6J mice (B). C, D: The bronchioli and bronchi of DBA/2J mice (C) were plugged with degenerate bronchial epithelial cells and neutrophils with higher degrees of degeneration, necrosis and loss of epithelial cells (arrows) two days after infection. In addition, the airways were surrounded by larger numbers of neutrophils and macrophages (asterisks). Airways of C57BL/6J mice (D) showed less damage with little or no plugging of airways. At that time point, the lungs of both strains had few infiltrations with lymphocytes. E, F: Four days after infection, virtually no extravasations of lymphocytes were detected in DBA/2J mice (E) whereas marked perivascular lymphocytic infiltrations (arrows) were observed in the pulmonary interstitium of C57BL/6J mice (F). Bars  =  250 µm (A, B), 25 µm (C, D) and 50 µm (E, F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654507&req=5

pone-0004857-g008: Severe damage of bronchial epithelia occurs in DBA/2J compared to C57BL/6J mice.DBA/2J (A, C, E) and C57BL/6J mice (B, D, F) were infected intra-nasally with 2×103 FFU of PR8 virus. Lung sections were stained with hematoxylin and eosin. A, B: Two days after infection, the lungs of DBA/2J mice (A) were more consolidated with higher numbers of plugged airways (arrows) than C57BL/6J mice (B). C, D: The bronchioli and bronchi of DBA/2J mice (C) were plugged with degenerate bronchial epithelial cells and neutrophils with higher degrees of degeneration, necrosis and loss of epithelial cells (arrows) two days after infection. In addition, the airways were surrounded by larger numbers of neutrophils and macrophages (asterisks). Airways of C57BL/6J mice (D) showed less damage with little or no plugging of airways. At that time point, the lungs of both strains had few infiltrations with lymphocytes. E, F: Four days after infection, virtually no extravasations of lymphocytes were detected in DBA/2J mice (E) whereas marked perivascular lymphocytic infiltrations (arrows) were observed in the pulmonary interstitium of C57BL/6J mice (F). Bars  =  250 µm (A, B), 25 µm (C, D) and 50 µm (E, F).
Mentions: Histological analyses of infected mice revealed striking differences between the tissue lesions in DBA/2J and C57BL/6J mice. The overall lung tissues were more densely consolidated with larger numbers of affected airways in DBA/2J mice compared to C57BL/6J mice (figure 8A, B). In both mouse strains, bronchial and bronchiolar epithelial cells showed degeneration, necrosis and loss with accumulation of sloughed cells and mostly degenerate neutrophils in the airway lumen at days 2 and 3 after infection. However, the degree of bronchial epithelial necrosis and airway plugging by cellular debris was much more pronounced in DBA/2J than C57BL/6J mice. This was accompanied by larger numbers of neutrophils and macrophages around the affected airways in DBA/2J mice (figure 8C, D). On the other hand, C57BL/6J mice developed a much stronger perivascular and peribronchial infiltration of lymphocytes at day 4 after infection (figure 8E, F). Alveolar epithelial cells were mostly unaffected. Few macrophages and virtually no plasma cells were seen in the lungs, with no differences between the two mouse strains at days 2 to 4 post infection.

Bottom Line: The genetic make-up of the host has a major influence on its response to combat pathogens.Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains.These findings indicate a major contribution of the genetic background of the host to influenza A virus infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Mouse Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus