A severe immune-system response aroused by the H1N1 influenza virus might explain why the 1918 Spanish flu was so deadly to animals and people, U.S. scientists reported on Wednesday.

    The study, appearing in the Sept. 27 advance online edition of the journal Nature, counters conventional thought about the 1918 flu that a secondary infection from another virus helped make the pandemic one of the deadliest in the modern era.

    According to the researchers from the University of Washington in Seattle, mice infected with the reconstructed 1918 influenza virus displayed "an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology."

    When studying the response of lung cells in mice infected with the virus, the researchers conducted a functional genomic analysis of those cells to monitor which genes were activated during the course of infection.

    They found that several genes related to immune responses were activated, as were genes related to programmed cell death, which occurs when the body kills off infected cells to stave off an infection.

    When the mice were infected with a virus containing all eight genes from the 1918 pandemic virus, they showed unabated signs of inflammation and cell-death within 24 hours after infection until death on the fifth day, the researchers said.

    "What we think is happening is that the host´s inflammatory response is being highly activated by the virus, and that response is making the virus much more damaging to the host," said John Kash, lead author of the study and an assistant professor at the University of Washington.

    "The host´s immune system may be overreacting and killing off too many cells, and that may be a key contributor to what makes this virus more pathogenic."

    The 1918 Spanish flu pandemic spread across the world in 1918 and 1919, and killed an estimated 25 million to 50 million people worldwide. Unlike seasonal flu that typically hits children and the elderly, Spanish flu affected many younger adults and people without immune-system problems.

    Modern researchers have long wondered why that influenza strain was so deadly, and why it affected many people.

    One theory that scientists have hypothesized is that a secondary infection followed the main influenza virus, striking people while their immune system was compromised from the flu.

    But this new research indicates that the interaction between the virus and the host´s immune system makes the 1918 flu especially deadly.

    These new findings may also help in the fight against the H5N1 highly pathogenic bird flu virus, which many feared could cause a new flu pandemic in humans, the scientists indicated.

    "With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and the potential of a worldwide pandemic, a comprehensive understanding of the global host response to the 1918 virus is crucial," the researchers wrote in the Nature paper.

    "Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel anti-viral therapies," they added.