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The PB2-E627K mutation attenuates viruses containing the 2009 H1N1 influenza pandemic polymerase.

Jagger BW, Memoli MJ, Sheng ZM, Qi L, Hrabal RJ, Allen GL, Dugan VG, Wang R, Digard P, Kash JC, Taubenberger JK - MBio (2010)

Bottom Line: The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years.The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths.Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential.

View Article: PubMed Central - PubMed

Affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,Maryland, USA.

ABSTRACT
The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.

No MeSH data available.


Related in: MedlinePlus

Clinical course of infection in mice as measured by weight loss. Mean percentage body weight loss from mean baseline weight of mice in each group inoculated with rescued A/New York/312/2001 (H1N1) (referred to as rNY312) or chimeric viruses containing the four RNP gene segments of different influenza viruses on the NY312 background (see key) from 0 to 14 days postinoculation (dpi). Groups of five 8- to 10-week-old female BALB/c mice were inoculated intranasally with 2 × 105 PFU of virus. Error bars represent SEM.
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f2: Clinical course of infection in mice as measured by weight loss. Mean percentage body weight loss from mean baseline weight of mice in each group inoculated with rescued A/New York/312/2001 (H1N1) (referred to as rNY312) or chimeric viruses containing the four RNP gene segments of different influenza viruses on the NY312 background (see key) from 0 to 14 days postinoculation (dpi). Groups of five 8- to 10-week-old female BALB/c mice were inoculated intranasally with 2 × 105 PFU of virus. Error bars represent SEM.

Mentions: To evaluate pathogenicity in vivo, the panel of viruses was intranasally inoculated into mice at a dose of 2 × 105 PFU. Daily weights of infected mice were obtained (Fig. 2) as an indicator of clinical disease, and lungs were collected to measure viral replication (Fig. 3) and observe histopathology (Fig. 4 and 5).


The PB2-E627K mutation attenuates viruses containing the 2009 H1N1 influenza pandemic polymerase.

Jagger BW, Memoli MJ, Sheng ZM, Qi L, Hrabal RJ, Allen GL, Dugan VG, Wang R, Digard P, Kash JC, Taubenberger JK - MBio (2010)

Clinical course of infection in mice as measured by weight loss. Mean percentage body weight loss from mean baseline weight of mice in each group inoculated with rescued A/New York/312/2001 (H1N1) (referred to as rNY312) or chimeric viruses containing the four RNP gene segments of different influenza viruses on the NY312 background (see key) from 0 to 14 days postinoculation (dpi). Groups of five 8- to 10-week-old female BALB/c mice were inoculated intranasally with 2 × 105 PFU of virus. Error bars represent SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2912665&req=5

f2: Clinical course of infection in mice as measured by weight loss. Mean percentage body weight loss from mean baseline weight of mice in each group inoculated with rescued A/New York/312/2001 (H1N1) (referred to as rNY312) or chimeric viruses containing the four RNP gene segments of different influenza viruses on the NY312 background (see key) from 0 to 14 days postinoculation (dpi). Groups of five 8- to 10-week-old female BALB/c mice were inoculated intranasally with 2 × 105 PFU of virus. Error bars represent SEM.
Mentions: To evaluate pathogenicity in vivo, the panel of viruses was intranasally inoculated into mice at a dose of 2 × 105 PFU. Daily weights of infected mice were obtained (Fig. 2) as an indicator of clinical disease, and lungs were collected to measure viral replication (Fig. 3) and observe histopathology (Fig. 4 and 5).

Bottom Line: The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years.The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths.Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential.

View Article: PubMed Central - PubMed

Affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,Maryland, USA.

ABSTRACT
The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus's recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.

No MeSH data available.


Related in: MedlinePlus