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Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

Amber Farooqui123, Alberto J Leon13, Yanchang Lei4, Pusheng Wang5, Jianyun Huang5, Raquel Tenorio1, Wei Dong1, Salvatore Rubino26, Jie Lin5, Guishuang Li1, Zhen Zhao1 and David J Kelvin123*

Author Affiliations

1 Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong, 515041, China

2 Department of Biomedical Sciences, University of Sassari, Sassari, Italy

3 Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, 101 College Street, Toronto, ON, M5G 1 L7, Canada

4 Division of Viral Hepatitis and Liver Failure, Infectious Disease Hospital, Nanchang University, Nanchang 9th Hospital, 167 Hongdu Middle Road, Nanchang, Jiangxi, 330002, China

5 Center for Disease Control and Prevention of Shantou, 58 Shanfen Road, Shantou, Guangdong, 515041, China

6 Center for Biotechnology Development and Biodiversity Research, University of Sassari, Sassari, Italy

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Virology Journal 2012, 9:104  doi:10.1186/1743-422X-9-104

Published: 6 June 2012

Abstract

Background

Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established.

Results

This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior.

Conclusions

The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

Keywords:
Pandemic H1N1 influenza; Viral heterogeneity; Clinical presentation; Host adaptation; Viral polymerase; Virulence; Pathogenesis