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Biosecurity Briefing
Study: Genetic Change in Amino Acid Could Lead to H5N1 Transmission Among Humans By Jennifer Nuzzo, October 12, 2007 A new study published in the October issue of the journal PLoS Pathogens provides experimental evidence that a genetic change in a single amino acid may contribute to the ability of avian H5N1 viruses to infect mammals, and ultimately may be the key to the eventual development of efficient human-to-human transmission.1 To date, “the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive.” Since the first recognition of human infection with H5N1 viruses in 1997, H5N1 viruses have caused more than 250 human cases but have not yet demonstrated efficient human-to-human transmission. Researchers have suggested for some time that H5N1 viruses that possess a specific hemaglutinin (HA) surface protein may be more capable of binding to and replicating in cells of the upper airways of mammals. If virus is able to replicate in the upper airways, it may have a greater potential to spread via coughing and sneezing, which could promote human-to-human transmission. However, the authors of the study point out that viruses isolated from humans with human receptor specificity “still failed to spread efficiently among humans.” This suggests that genetic changes in “viral proteins other than HA might be required for the efficient growth and person-to-person transmission of avian H5N1 influenza virus in humans.”1 To determine what other genetic changes are needed to make H5N1 viruses efficiently transmissible among humans, the team of investigators from the United States, Japan, and Vietnam compared two human H5N1 influenza viruses that were isolated from the lower respiratory tract and the upper airway of a single patient for their ability to grow in cells and in the respiratory tracts of mice. Although the two viruses were found to differ by six amino acids, the research team was interested specifically in the relative effects of a single amino acid difference between viruses isolated from the upper and lower airways of the patient: viruses that were isolated from the upper airway of the patient had possessed the amino acid lysine (Lys) at location 627 on the PB2 protein (a protein involved in viral replication), whereas those isolated from the lower airway were found to have the amino acid glutamic acid at PB-627.1 The investigators found that the viruses isolated from the upper airway of the patient, which contained the amino acid lysine (Lys) at PB2-627, replicated more efficiently in more types of cells of the mammalian respiratory tract and at lower temperatures than the viruses with the amino acid glutamic acid (Glu) at PB2-627. The authors conclude that 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.” They further conclude that “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 in transmission.”1 As reported by CIDRAP News, the study’s lead author Yoshihiro Kawaoka said that “H5N1 viruses circulating now are more ‘mammalian-like’ than the ones that circulated in 1997, when the first human infections were identified.” He noted, however, that “additional genetic changes are probably needed to equip the H5N1 virus with full pandemic potential.” Still, he believes that “it's only a matter of time before the H5N1 virus evolves into a strain that's capable of launching a pandemic.”2 References
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