Possible origin of current influenza A H1N1 viruses.

The ongoing outbreak of swine-origin infl uenza A H1N1 in Mexico, the USA, and 40 other countries reminds us that the risk of an infl uenza pandemic is high and will persist in the future. The fi rst two cases of H1N1 infection in Southern California, USA, were reported on April 21, 2009. According to WHO’s estimation, seasonal infl uenza epidemics result in about 3 million to 5 million cases of severe illness worldwide, and about 250 000 to 500 000 of the people with severe illness die each year from complications of infl uenza. In pandemic years, such deaths could easily exceed millions and cost billions of US dollars every year. Compared with avian infl uenza H5N1 and seasonal infl uenza epidemics, the 2009 outbreak of H1N1 is relatively mild in terms of mortality rate. Scientists from the US Centers for Disease Control and Prevention submitted to GenBank (on April 27, 2009) the fi rst set of completed coding sequences for the new infl uenza A virus, A/California/04/2009 (H1N1), isolated from a 10-year-old boy in California on April 1, 2009. By use of the Basic Local Alignment Search Tool program, we compared the nucleotide sequence of the eight gene segments of this newly isolated virus with hundreds of other available infl uenza sequences in GenBank and listed the most similar ones in the table. We found that circulating strains of the H1N1 viruses isolated from diff erent countries were essentially identical, and all eight gene segments of the new infl uenza A virus (A/California/04/2009) possibly originated from swine infl uenza viruses (table). Sequence analysis also suggests that six gene segments (PB2, PB1, PA, HA, NP, and NS1) of circulating H1N1 viruses probably came from swine infl uenza H1N2 viruses circulating in the USA from 1999 to 2001 and two gene segments (NA and M1) possibly originated from swine infl uenza H1N1 viruses circulating in Europe from 1985–98. Important questions are when, where, and how the swine infl uenza viruses circulating in the USA 8 years ago were mixed with the swine infl uenza viruses circulating in Europe 11 years ago and mutated to form the current reassortant H1N1 viruses? These events established that the future pandemic infl uenza could potentially come from reassortant viruses originating from birds, animals, or people in diff erent areas of the world. The key factor leading to most deaths in the previous three infl uenza pandemics (the Spanish fl u of 1918–19, the Asian fl u of 1957–58, and the Hong Kong fl u of 1968–69) was the infl uenza-related secondary bacterial pneumonia caused by common upper respiratory tract bacteria. Infl uenza virus infection and the secondary bacterial pneumonia in animals were summarised in a recent review article. The severity of secondary bacterial pneumonia after infl uenza virus infection is dependent on viral and bacterial pathogenic factors and their interactions with host immune responses. To reduce the risk of a high mortality rate from potential pandemic infl uenza, it is important to understand which pathogenic factors (either viral, bacterial, or host) contribute the most to secondary bacterial pneumonia and severe respiratory distress. Therefore, infl uenza pandemic preparedness should include the development of new drugs and vaccines for effi cient control and treatment of the secondary bacterial pneumonia. Continued circulation of avian and swine infl uenza viruses in Asia and other areas of the world shows that PB2 PB1 PA HA NP NA M1 NS1