RESEARCH ABOUT THE INFLUENZA VIRUS

Mutations and Strains

"The influenza virus genome has remarkable plasticity because of a high mutation rate and its segmentation into 8 separate RNA molecules. This segmentation allows frequent genetic exchange by segment reassortment in hosts co-infected with 2 different influenza viruses."

In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute, Harbin, China and Professor Robert Webster of the St Jude Children's Research Hospital, Memphis, Tennessee, reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity" Results reported by Dr. Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks.

In May 2005, the occurrence of avian influenza in pigs ("swine flu") in Indonesia was reported. Along with the continuing pattern of virus circulation in poultry, the occurrence in swine raises the level of concern about the possible evolution of the virus into a strain capable of causing a global human influenza pandemic. Health experts say pigs can carry human influenza viruses, which can combine (i.e. exchange homologous genome sub-units by genetic reassortment.) with the avian virus, swap genes and mutate into a form which can pass easily among humans.

In July 2005, a death in Jakarta was the first confirmed human fatality in Indonesia. The deaths of two children, neither of whom were reported to have had close contact with poultry, further raised concerns of human-to-human transmission.  As of July 2005, most human cases of avian influenza in East Asia have been attributed to consumption of diseased poultry. Person-to-person transmission has not been unequivocally confirmed in the outbreaks in East Asia.

On August 3, 2005, the WHO said it was following closely reports from China that at least 38 people have died and more than 200 others have been made ill by a swine-borne virus in Sichuan Province. Sichuan Province, where infections with Streptococcus suis have been detected in pigs in a concurrent outbreak, has one of the largest pig populations in China. The outbreak in humans has some unusual features and is being closely followed by the WHO. At that time, Chinese authorities say they have found no evidence of human-to-human transmission . On September 29, 2005, David Nabarro, the newly appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill 5 to 150 million people. Also, due to a bipartisan effort of the United States Senate, $4 billion dollars was appropriated to develop vaccines and treatments for Avian influenza.

In 2004 and 2005, 118 people are known to have been infected with the H5N1 virus and 61 of them died. The mortality rate of this virus is as high as that of the virus H1N1 that caused the Spanish Flu of 1918, which killed over 20 million people world wide. One of the major differences between H1N1 of 1918 and the current H5N1 is the fact that the latter is not (yet) transmissible between humans. Until recently, that prevented the H5N1 virus from becoming a pandemic. Recent research of Taubenberger et al {Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005 Oct 6;437(7060):889-893} showed that the 1918 virus like H5N1 was an avian virus. Furthermore, Tumpey and colleagues {Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science. 2005 Oct 7;310(5745):77-80} who reconstructed the H1N1 virus of 1918 come to the conclusion that it is especially the polymerase genes and the HA and NA genes that caused the extreme virulence of this virus. The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the avian influenza viruses. Human forms of seven of the ten amino acids have already been identified in currently circulating H5N1. It is not unlikely that also the other mutations eventually will surface and make the H5N1 virus better suited for human-to-human transmission.

Another important factor is the change of the HA protein to a binding preference for alpha 2,6 sialic acid (the major form in the human respiratory tract). In avian virus the HA protein preferentially binds to alpha 2,3 sialic acid, which is the major form in the avian enteric tract. It has been shown that only a single amino acid change can result in the change of this binding preference. Altogether it seems that only a few mutations are needed to make the H5N1 avian influenza virus a pandemic virus like the one of 1918.

"In Vietnam, scientists at the Ho Chi Minh Pasteur Institute who have been studying the genetic make up of H5N1 samples taken from people and poultry said it had undergone several mutations. 'There has been a mutation allowing the virus to (replicate) effectively in mammal tissue and become highly virulent.