More evidence that the new H1N1 virus is more dangerous than seasonal flu: The new Kawaoka paper

A paper has just come out from Dr. Yoshihiro Kawaoka’s group describing their findings regarding the respective dangers of the new, pandemic H1N1 and seasonal flu (see reference below). Although this work supports two recent studies with ferrets suggesting that the new H1N1 causes more illness than seasonal flu, the new study provides additional insights into the pathology caused by H1N1.

Mice, ferrets, monkeys and pigs were given either the new H1N1 or a seasonal H1N1 intranasally. The following new H1N1 strains were used:

  • A/California/04/09
  • A/Wisconsin/WSLH049/09
  • A/Wisconsin/WSLH34939/09
  • A/Netherlands/603/09
  • A/Osaka/164/09

These strains were all isolated from individuals with mild disease except A/Wisconsin/WSLH34939/09 which came from a person who had been hospitalised.

In mice, ferrets and monkeys the new H1N1 strains caused more severe disease than the seasonal H1N1 strain. However, in pigs, few clinical signs were observed with the new H1N1 suggesting that the virus may be spread asymptomatically in this species.

The amount of virus necessary to kill 50% of the mice was examined with the different strains. Less virus was required to kill mice with most of the new H1N1 strains than with the seasonal H1N1 . A/Wisconsin/WSLH049/09 was equally lethal to the mice as seasonal H1N1. Of the new H1N1 strains, A/Wisconsin/WSLH34939/09 was the most lethal. This is the strain isolated from an individual that had been hospitalised.

Striking differences in lung pathology in mice, monkeys and ferrets were observed between animals that received the new H1N1 virus as compared to animals that received seasonal H1N1. In particular, the lungs of monkeys that received the new H1N1 exhibited similar pathological changes to those seen in animals exposed to H5N1.

Transmission between ferrets by aerosol droplets was similar in animals infected with seasonal or pandemic H1N1.

One notable, and surprising, finding of this study was that neutralising activity was found in sera collected from the residents of nursing home that were born before 1920, but none in those born after. Thus, only those exposed to the 1918 virus are likely to have antibodies that recognise the new H1N1. Therefore, the relative paucity of deaths among people in the 60 to 89 age range cannot be explained by exposure to a virus that conferred cross-protection to the new H1N1.

In comparing this study with the two previous studies using ferrets, I am again struck by the parallels between the severity of disease observed in its human host and the ability of particular isolates to cause disease in animals. A/Wisconsin/WSLH34939/09, which was the only strain isolated from an individual who had been hospitalised, was the most lethal in mice. This adds further support for my hypothesis that the new H1N1 is unstable and causing variable disease due to variations in the virus itself.

Future studies explicitly comparing pathology in animals caused by virus isolated from patients with different clinical outcomes may be informative. If this association holds up, sequence analysis may provide clues into which variants of the virus are most likely to cause severe disease.

Reference:

Itoh, et al. (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature, doi:10.1038/nature08260

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