The virus - known as Spanish flu - infected up to a billion people in 1918 and killed between 20 million and 40 million victims in a global epidemic that has remained unexplained for the past 80 years.
Now a study of a virus related to Spanish flu has found it is capable of causing widespread infection in the body rather than just affecting the tissues of the respiratory tract.
Such a ''systemic'' infection would have been far deadlier and, although it has not been documented in human flu, it is known to occur when certain strains of the virus infect other animals, such as chickens.
The discovery has implications for the emergence of new strains of flu which could cause catastrophic epidemics today, said Yoshihiro Kawaoka, a virologist from the University of Wisconsin at Madison.
''This could be another important indicator of whether a virus is dangerous and potentially lethal,'' said Dr Kawaoka.
Dr Kawaoka studied a virus closely related to the 1918 strain, which appeared nearly a decade later. He found that the virus could replicate in a wide variety of human tissues.
For a flu virus to infect a human cell it has to chop in half one of its surface proteins, called haemagglutinin. Normally only lung and respiratory tissues carry the necessary enzymes that can do this, which is why lungs are so vulnerable to attack.
Dr Kawaoka, however, demonstrates in the current issue of the scientific journal Proceedings of the National Academy of Sciences that a number of different tissues in the body can cleave the haemagglutinin protein and thereby allow widespread infection of the body.
Changes to the surface proteins of flu viruses occur frequently, which is the reason why flu vaccines have only limited use. Scientists fear that if the 1918 flu virus was capable of changing into a systemic infection, the same mutation could happen again.
John Skehel, director of the National Institute for Medical Research in London and an expert on the flu virus, said: ''It might give us another clue about why the 1918 epidemic was so bad."Reuse content