Genes that gave 1918 flu virus extraordinary virulence identified

December 30th, 2008 - 11:47 am ICT by ANI  

Washington, December 30 (ANI): Researchers at the University of Wisconsin-Madison have identified a set of three genes that gave the 1918 virus behind the “Spanish flu”, which claimed about 20 to 50 million lives 90 years ago, the extraordinary virulence.
Virologists Yoshihiro Kawaoka and Tokiko Watanabe have revealed that they did so by mixing and matching a contemporary flu virus with the Spanish flu virus.
Writing about their work in the Proceedings of the National Academy of Sciences, the researchers have revealed that the genes identified by them are those that gave the virus the capacity to reproduce in lung tissue.
“Conventional flu viruses replicate mainly in the upper respiratory tract: the mouth, nose and throat. The 1918 virus replicates in the upper respiratory tract, but also in the lungs,” causing primary pneumonia among its victims, says Kawaoka, an internationally recognized expert on influenza and a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine.
“We wanted to know why the 1918 flu caused severe pneumonia,” the researcher added.
The researchers highlighted the fact that autopsies of 1918 flu victims often revealed that fluid-filled lungs severely damaged by massive haemorrhaging.
They said that they started their study with the assumption that the ability of the virus to take over the lungs might be associated with the pathogen’’s high level of virulence, but the genes that conferred that ability were unknown.
Kawaoka believes that finding the complex and its role in orchestrating infection in the lungs may be significant for the identification of the potential virulence factors in new pandemic strains of influenza.
He says that the complex could also become a target for a new class of antiviral drugs, which is urgently needed because vaccines are unlikely to be produced fast enough at the outset of a pandemic to blunt its spread.
With a view to identify the gene or genes that enabled the virus to invade the lungs, the researchers blended genetic elements from the 1918 flu virus with those of a currently circulating avian influenza virus, and tested the variants on ferrets, an animal that mimics human flu infection.
They revealed that substituting single genes from the 1918 virus onto the template of a much more benign contemporary virus yielded agents that could only replicate in the upper respiratory tract.
Kawaoka and his colleagues observed that there were three genes that acted in concert with another key gene to allow the virus to efficiently colonize lung cells, and make RNA polymerase, a protein necessary for the virus to reproduce.
“The RNA polymerase is used to make new copies of the virus,” Kawaoka says.
He revealed that in the absence of that protein, the virus was unable to make new virus particles and spread infection to nearby cells.
He also revealed that tests on ferrets showed that most of the hybrid viruses only infected their nasal passages and didn”t cause pneumonia, but one that could infect the lungs carried the RNA polymerase genes from the 1918 virus, which allowed the virus to make the key step of synthesizing its proteins.
The RNA polymerase is used to make copies of the virus once it has entered a host cell. (ANI)

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