Highly pathogenic avian H5N1 influenza viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33°C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2–627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human receptors.
Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice
PLoS Pathogens 2007 3 (10) e133
What does this all mean?
The H5N1 influenza virus (formerly known as “bird flu”) has mutated to infect people more easily, although it still has not transformed into a pandemic strain. In order to acquire the capacity for efficient human-to-human transmission, H5N1 avian influenza viruses must undergo a series of genetic changes resulting in the ability to replicate at lower temperatures, in a wider range of cell types, to recognize human receptors, and other unknown phenotypic changes controlled by virus proteins. Birds usually have a body temperature of 41°C, and humans 37°C. The human nose and throat, where flu viruses usually enter, is usually around 33°C, so the virus doesn’t grow well in the nose or throat of humans. This research identifes a mutation which allows H5N1 to replicate in the cooler temperatures of the human upper respiratory tract. The H5N1 viruses circulating in Europe and Africa all have this mutation. What we don’t know at present is how many additional mutations are needed for these humanized viruses to become a pandemic strain, or how long that process will take.
Although it has not been in the news much recently, the highly pathogenic avian influenza A virus subtype H5N1 has been endemic in some bird species since its emergence in 1996 and its ecology, genetics and antigenic properties continue to evolve. This has allowed diverse virus strains to emerge in endemic areas with altered receptor specificity, including a new H5 sublineage with enhanced binding affinity to the human-type receptor. The pandemic potential of H5N1 viruses is alarming and may be increasing. This article reviews the complex and changing nature of the H5N1 virus that may contribute to the emergence of pandemic strains – with really serious consequences.
