On January 8, 2014, an Albertan resident died after contracting H5N1 avian influenza. This was the first H5N1 related death in North America. Federal and provincial health officials were quick to reassure the public that person-to-person transmission of H5N1 influenza is “extremely rare”. In fact, of the 386 H5N1-related deaths reported to the World Health Organization (WHO) since 2003, almost all involved close contact with birds. Sure enough, later reports suggested that the Albertan resident may have contracted the virus whilst passing through an illegal bird market in Beijing.
But could H5N1 be transmitted between humans? Researchers at the Erasmus Medical Center sought to answer this question and on June 22, 2012 they published a highly controversial paper detailing how they re-engineered the H5N1 virus so that it could be transmitted between humans.
Before we discuss this exciting study, we need to take a brief look at the structure and life cycle of the Influenza virus. There are 3 subtypes of the Influenza virus: Influenza A, B and C. H5N1 is an Influenza A virus and these viruses have 2 types of proteins on their surface: Hemagglutinin and Neuraminidase. There are 18 known forms of Hemagglutinin and 11 known forms of Neuraminidase. A H5N1 virus has a type 5 Hemaggluttinin and a type 1 Neuraminidase on its surface.
Hemagglutinin is the protein responsible for viral cell entry. On the surface of the cells of our respiratory system are molecules called Sialic acid. Hemagglutinin on the surface of the virus binds to Sialic acid on the cell, triggering the cell to engulf the virus. Upon entry into the cell, the virus takes over and using an enzyme called a polymerase it makes many copies of itself. Eventually the cell bursts and the virus copies are released.
Influenza A virus: Courtesy of www.flickr.com
In the experiment, the researchers made H5N1 virus particles that were transmissible between ferrets (often used as an animal model for human Influenza infection). The researchers began by introducing 3 substitution mutations that had been identified in other highly transmissible Influenza viruses. A substitution mutation is a type of mutation that exchanges one base for another in the nucleotide sequence of a gene. Mutations change the structure of the associated protein. In this case, the mutated virus’s had altered Hemagglutinin on their surface.
The mutated virus’s were then manually placed in the nose of ferrets. Following infection, the researchers swabbed the noses of the infected ferrets and proceeded to infect another group of ferrets. This process was repeated multiple times. By the 10th cycle the mutant H5N1 was airborne and was being transmitted between ferrets in different cages.
The genome (genetic material) of the mutant H5N1 was analyzed and it was found that a total of 5 mutations, 4 mutations in Hemagluttinin and 1 mutation in the polymerase, was necessary for the virus to become transmissible between humans. Researchers at Cambridge University looked for the same mutations in naturally occurring H5N1 virus’s. They found that the mutations existed individually or in pairs, but never all together in one virus.
So, is a H5N1 pandemic eminent? This is still unknown, but researchers have taken important steps in better understanding the mechanism of transmission of H5N1 Influenza virus.
For a more detailed look at the lifecycle of Influenza viruses, check out this video.
Fardowsa Yusuf
References
http://arstechnica.com/science/2012/06/controversial-h5n1-bird-flu-papers-published-fuels-fears-of-airborne-mutations/
