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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.

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DBA/2J mice exhibit a stronger inflammatory response than C57BL/6J mice.DBA/2J (checked bars) and C57BL/6J mice (black bars) were infected intra-nasally with 2├Ś103 FFU of PR8 virus. Bronchio-alveolar lavage (BAL) was collected from non-infected controls (c) or at the indicated days (d1, d2, d3, d4) post infection, and the concentration of cytokines (A) or chemokines (B) was determined. Expression of cytokines and chemokines was determined by real-time PCR (C). Each time point represents the mean value ┬▒SEM of 7 mice per group for (A) and (B), and of 10 mice per group for (C). DBA/2J and C57BL/6J mice were compared for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p value<0.05; **: p<0.01; ***: p value<0.001.
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pone-0004857-g007: DBA/2J mice exhibit a stronger inflammatory response than C57BL/6J mice.DBA/2J (checked bars) and C57BL/6J mice (black bars) were infected intra-nasally with 2├Ś103 FFU of PR8 virus. Bronchio-alveolar lavage (BAL) was collected from non-infected controls (c) or at the indicated days (d1, d2, d3, d4) post infection, and the concentration of cytokines (A) or chemokines (B) was determined. Expression of cytokines and chemokines was determined by real-time PCR (C). Each time point represents the mean value ┬▒SEM of 7 mice per group for (A) and (B), and of 10 mice per group for (C). DBA/2J and C57BL/6J mice were compared for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p value<0.05; **: p<0.01; ***: p value<0.001.

Mentions: During the course of an infection, the host responds with the production of various cytokines and chemokines which then activate the different components of the innate and adaptive immune system. Therefore, the presence of several cytokines and chemokines was studied in broncho-alveolar lavages (BAL) of infected C57BL/6J and DBA/2J mice. In total, 22 cytokines and chemokines were analyzed. As shown in figure 7A, the cytokines Il5, Il6, Il1╬▒, Il12, and Csf3 (G-CSF) were elevated in the lungs of infected compared to non-infected mice. In all cases, levels of expression were higher in DBA/2J than in C57BL/6J mice. Similarly, the chemokines Ccl2 (MCP-1), Ccl3 (MIP-1╬▒), Ccl5 (RANTES), Cxcl1 (KC), Cxcl2 (MIP-2), Cxcl9 (MIG), and Cxcl10 (IP-10) were higher in infected, compared to non-infected DBA/2J and C57BL/6J mice (figure 7B). DBA/2J mice exhibited a higher level of expression for all chemokines tested. Also, at the transcriptional level, elevated expression of chemokines and cytokines in DBA/2J compared to C57BL/6J mice was observed by real-time PCR analysis for Ccl2, Ccl3, Cxcl10 and Il6 (figure 7C).


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)

DBA/2J mice exhibit a stronger inflammatory response than C57BL/6J mice.DBA/2J (checked bars) and C57BL/6J mice (black bars) were infected intra-nasally with 2├Ś103 FFU of PR8 virus. Bronchio-alveolar lavage (BAL) was collected from non-infected controls (c) or at the indicated days (d1, d2, d3, d4) post infection, and the concentration of cytokines (A) or chemokines (B) was determined. Expression of cytokines and chemokines was determined by real-time PCR (C). Each time point represents the mean value ┬▒SEM of 7 mice per group for (A) and (B), and of 10 mice per group for (C). DBA/2J and C57BL/6J mice were compared for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p value<0.05; **: p<0.01; ***: p value<0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654507&req=5

pone-0004857-g007: DBA/2J mice exhibit a stronger inflammatory response than C57BL/6J mice.DBA/2J (checked bars) and C57BL/6J mice (black bars) were infected intra-nasally with 2├Ś103 FFU of PR8 virus. Bronchio-alveolar lavage (BAL) was collected from non-infected controls (c) or at the indicated days (d1, d2, d3, d4) post infection, and the concentration of cytokines (A) or chemokines (B) was determined. Expression of cytokines and chemokines was determined by real-time PCR (C). Each time point represents the mean value ┬▒SEM of 7 mice per group for (A) and (B), and of 10 mice per group for (C). DBA/2J and C57BL/6J mice were compared for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p value<0.05; **: p<0.01; ***: p value<0.001.
Mentions: During the course of an infection, the host responds with the production of various cytokines and chemokines which then activate the different components of the innate and adaptive immune system. Therefore, the presence of several cytokines and chemokines was studied in broncho-alveolar lavages (BAL) of infected C57BL/6J and DBA/2J mice. In total, 22 cytokines and chemokines were analyzed. As shown in figure 7A, the cytokines Il5, Il6, Il1╬▒, Il12, and Csf3 (G-CSF) were elevated in the lungs of infected compared to non-infected mice. In all cases, levels of expression were higher in DBA/2J than in C57BL/6J mice. Similarly, the chemokines Ccl2 (MCP-1), Ccl3 (MIP-1╬▒), Ccl5 (RANTES), Cxcl1 (KC), Cxcl2 (MIP-2), Cxcl9 (MIG), and Cxcl10 (IP-10) were higher in infected, compared to non-infected DBA/2J and C57BL/6J mice (figure 7B). DBA/2J mice exhibited a higher level of expression for all chemokines tested. Also, at the transcriptional level, elevated expression of chemokines and cytokines in DBA/2J compared to C57BL/6J mice was observed by real-time PCR analysis for Ccl2, Ccl3, Cxcl10 and Il6 (figure 7C).

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