2009 Pandemic H1N1 Influenza Virus Replicates in Human Lung Tissues

The newly emerged swine-origin influenza A virus (2009 pandemic H1N1) has spread globally in the months following the initial April 2009 outbreak in Mexico and California, USA[1, 2], causing the first influenza pandemic of the 21st century, as declared by the World Health Organization (WHO) on June 11, 2009 (http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/). Initial genetic analysis found that the current pandemic strain contains viral segments from swine, human and avian hosts, obtained through multiple reassortment events which cannot be clearly defined at this time[3, 4]. At this stage overall infection severity is mild, according to WHO epidemiological data (http://www.who.int/csr/resources/publications/swineflu/technical_consultation_2009_05_06/en/index.html)[5]. However, 3917 fatal cases have been observed as of 20 September 2009, according to the WHO. The rapid worldwide transmission, combined with the chance of unpredictable adaptation mutations being introduced through continued circulation in humans, the possibility of further reassortment with current seasonal or avian influenza viruses, and the lack of pre-existing immunity to this virus in the general population pose uncertainties regarding the potential severity in humans in the coming pandemic phases. Experience from previous pandemics suggests that severity may change following initial human circulation [6, 7]. Experiments with mice, ferrets, pigs and non-human primates found that pandemic H1N1 virus is able to replicate in the lung tissues of infected animals[8–10], an attribute shared with the highly pathogenic H5N1 viruses but different to the seasonal human influenza viruses, which have only limited replication abilities in lung tissues[11, 12]. The observation of some severe, and even fatal, outcomes in patients without underlying health problems also poses concerns regarding the mechanism of pathogenesis of 2009 pandemic H1N1. The factors that contribute to the discrepancies between animal pathogenicity data and clinical presentation in most human cases are not clear at this stage. Information on pandemic H1N1 virus replication and growth properties in human tissues will be important for understanding the virulence potential of this virus in humans. This study used surgically-removed lung tissues to evaluate viral gene expression in an ex vivo system and found that the current pandemic strain has a greater potential to replicate in human lung tissues, a property similar to that of highly pathogenic H5N1 viruses.