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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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Different inbred laboratory mouse strains exhibit variable kinetics of weight loss and survival after infection with Influenza A virus.C57BL/6J, DBA/2J, FVB/NJ, CBA/J, BALB/cByJ, A/J and SJL/JOrlCrl mice were infected intra-nasally with 2×103 FFU of PR8 virus. Weight loss and survival of infected mice was followed over a period of 14 days. Mortality also includes mice that were sacrificed because they had lost more than 25% of body weight. Mean percent of body weight change (±SEM) for each group of inbred strains is shown. For DBA/2J and C57BL/6J mice, data are from two independent experiments. Statistical analysis of pair wise comparisons for all strains and days are presented in table 1.
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pone-0004857-g001: Different inbred laboratory mouse strains exhibit variable kinetics of weight loss and survival after infection with Influenza A virus.C57BL/6J, DBA/2J, FVB/NJ, CBA/J, BALB/cByJ, A/J and SJL/JOrlCrl mice were infected intra-nasally with 2×103 FFU of PR8 virus. Weight loss and survival of infected mice was followed over a period of 14 days. Mortality also includes mice that were sacrificed because they had lost more than 25% of body weight. Mean percent of body weight change (±SEM) for each group of inbred strains is shown. For DBA/2J and C57BL/6J mice, data are from two independent experiments. Statistical analysis of pair wise comparisons for all strains and days are presented in table 1.

Mentions: Seven different inbred laboratory mouse strains were infected with a dose of 2×103 FFU of influenza A virus PR8 (H1N1) and followed for a period of 14 days after infection. As illustrated in figure 1, large differences in the kinetics of weight loss and survival were observed. Most notably, mice from two inbred strains, DBA/2J and A/J, lost weight very rapidly and died within the first seven days after infection, or were sacrificed because weight loss exceeded 25%. All infected mice from the other strains survived this infection dose. The weight loss in the highly susceptible strains DBA/2J and A/J mouse strains was significantly different compared to all resistant strains (table 1). The surviving strains exhibited three principle types of weight loss kinetics. BALB/cByJ, CBA/J and SJL/JOrlCrl rapidly lost weight within the first days after infection until about day 6 to 7 and then slowly recovered, with SJL/JOrlCrl being the least affected in this group (figure 1). C57BL/6J mice did not lose weight early after infection but rapidly lost weight after day 4 until day 7 and then quickly recovered (figure 1). The weight loss in C57BL/6J mice was significantly different to the BALB/c mouse strain on days 2–4 but not at later time points (table 1). FVB/NJ mice were the least affected by this infection dose (figure 1, table 1). The weight change in infected DBA/2J and C57BL/6J mice was significantly different compared to mock-infected mice, instilled with PBS only (data not shown).


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)

Different inbred laboratory mouse strains exhibit variable kinetics of weight loss and survival after infection with Influenza A virus.C57BL/6J, DBA/2J, FVB/NJ, CBA/J, BALB/cByJ, A/J and SJL/JOrlCrl mice were infected intra-nasally with 2×103 FFU of PR8 virus. Weight loss and survival of infected mice was followed over a period of 14 days. Mortality also includes mice that were sacrificed because they had lost more than 25% of body weight. Mean percent of body weight change (±SEM) for each group of inbred strains is shown. For DBA/2J and C57BL/6J mice, data are from two independent experiments. Statistical analysis of pair wise comparisons for all strains and days are presented in table 1.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654507&req=5

pone-0004857-g001: Different inbred laboratory mouse strains exhibit variable kinetics of weight loss and survival after infection with Influenza A virus.C57BL/6J, DBA/2J, FVB/NJ, CBA/J, BALB/cByJ, A/J and SJL/JOrlCrl mice were infected intra-nasally with 2×103 FFU of PR8 virus. Weight loss and survival of infected mice was followed over a period of 14 days. Mortality also includes mice that were sacrificed because they had lost more than 25% of body weight. Mean percent of body weight change (±SEM) for each group of inbred strains is shown. For DBA/2J and C57BL/6J mice, data are from two independent experiments. Statistical analysis of pair wise comparisons for all strains and days are presented in table 1.
Mentions: Seven different inbred laboratory mouse strains were infected with a dose of 2×103 FFU of influenza A virus PR8 (H1N1) and followed for a period of 14 days after infection. As illustrated in figure 1, large differences in the kinetics of weight loss and survival were observed. Most notably, mice from two inbred strains, DBA/2J and A/J, lost weight very rapidly and died within the first seven days after infection, or were sacrificed because weight loss exceeded 25%. All infected mice from the other strains survived this infection dose. The weight loss in the highly susceptible strains DBA/2J and A/J mouse strains was significantly different compared to all resistant strains (table 1). The surviving strains exhibited three principle types of weight loss kinetics. BALB/cByJ, CBA/J and SJL/JOrlCrl rapidly lost weight within the first days after infection until about day 6 to 7 and then slowly recovered, with SJL/JOrlCrl being the least affected in this group (figure 1). C57BL/6J mice did not lose weight early after infection but rapidly lost weight after day 4 until day 7 and then quickly recovered (figure 1). The weight loss in C57BL/6J mice was significantly different to the BALB/c mouse strain on days 2–4 but not at later time points (table 1). FVB/NJ mice were the least affected by this infection dose (figure 1, table 1). The weight change in infected DBA/2J and C57BL/6J mice was significantly different compared to mock-infected mice, instilled with PBS only (data not shown).

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