Researchers from the US and Japan studying the new H1N1 pandemic flu virus suggest that it is more virulent than previously thought. They found the virus seizes hold in cells deep inside the lungs, leading to pneumonia and in more severe cases, death, whereas seasonal flu viruses only infect cells in the upper respiratory tract.

University of Wisconsin-Madison virologist and leading authority on influenza, Dr Yoshihiro Kawaoka led the international team of researchers in a detailed investigation of the pandemic H1N1 virus and its pathogenic properties and wrote about their findings in a fast-track report published online on 13 July in the journal Nature.

The researchers wrote that the spread of the new strain of influenza A virus that the World Health Organization declared a global pandemic on 11 June is probably due to the fact there are many humans with little or no pre-existing immunity.

Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and a professor at the University of Tokyo, said this virus was misunderstood in that many people were under the impression it was like seasonal influenza, but this study shows that is not the case:

“There is clear evidence the virus is different than seasonal influenza,” said Kawaoka.

The ability to infect deep inside the lungs is similar to that of other pandemic viruses, including the 1918 strain that killed tens of millions of people around the world, said the researchers.

It also bears other similarities to the 1918 strain in that people born before 1918 have antibodies that protect against today’s pandemic strain.

Kawaoka said it is also possible that the virus could evolve new properties.

For the study, the researchers infected mice, ferrets and non-human primates with pandemic H1N1 and seasonal flu from samples obtained from human patients in California, Wisconsin, the Netherlands and Japan.

They found that the pandemic flu strain replicated much more efficiently in the respiratory system than the seasonal flu. It also caused severe lesions in the lungs, closely resembling the damage caused by other pandemic strains.

Kawaoke said:

“The H1N1 virus replicates significantly better in the lungs.”

Also, using specific-pathogen-free miniature pigs, the researchers found that the virus spread in pigs without showing any clinical symptoms.

The team were also able to assess the immune response of different people to the new virus. They found that those who had been exposed to the 1918 strain (all now in advanced old age) had antibodies that neutralized the novel pandemic H1N1 virus.

“The people who have high antibody titers are the people born before 1918,” said Kawaoke.

But, although the discovery that the new H1N1 strain is potentially more dangerous than previously reported is a matter for concern, Kawaoke said the good thing was that it does respond to existing and experimental antivirals and these provide a potentially effective first line of defence against the virus.

From a public health point of view, a first line of defence is important because it slows down the spread of a virus for a few months while a vaccine is being mass produced.

There are three approved antivirals on the market and the team tested two of them and also two experimental ones that are not yet approved. They tested the drugs on mice and found that:

“The existing and experimental drugs work well in animal models, suggesting they will work in humans,” said Kawaoka.

The research was sponsored by the U.S. National Institutes of Health, and the Japanese Ministry of Education, Culture, Sports, Science and Technology.

“In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.”
(near-final version)
Yasushi Itoh, Kyoko Shinya, Maki Kiso, Tokiko Watanabe, Yoshihiro Sakoda, Masato Hatta, Yukiko Muramoto, Daisuke Tamura, Yuko Sakai- Tagawa, Takeshi Noda, Saori Sakabe, Masaki Imai, Yasuko Hatta, Shinji Watanabe, Chengjun Li, Shinya Yamada, Ken Fujii, Shin Murakami, Hirotaka Imai, Satoshi Kakugawa, Mutsumi Ito, Ryo Takano, Kiyoko Iwatsuki-Horimoto, Masayuki Shimojima, Taisuke Horimoto, Hideo Goto, Kei Takahashi, Akiko Makino, Hirohito Ishigaki, Misako Nakayama, Masatoshi Okamatsu, Kazuo Takahashi, David Warshauer, Peter A. Shult, Reiko Saito, Hiroshi Suzuki, Yousuke Furuta, Makoto Yamashita, Keiko Mitamura, Kunio Nakano, Morio Nakamura, Rebecca Brockman-Schneider, Hiroshi Mitamura, Masahiko Yamazaki, Norio Sugaya, M. Suresh, Makoto Ozawa, Gabriele Neumann, James Gern, Hiroshi Kida, Kazumasa Ogasawara & Yoshihiro Kawaoka.
Nature advance online publication 13 July 2009.

Source: UW-Madison.

Written by: Catharine Paddock, PhD