An analysis of “Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt”

Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt” by Watanabe et al. was recently published in PLoS Pathogens [hat-tip, Goju]. This paper describes changes in the ability of the H5N1 virus to bind to human receptors in the respiratory system and the possible role of these changes in the relatively large number of human cases of H5N1 in Egypt.

There were a number of interesting findings. But first, it is worth recording the source of the data.

From the paper:

We studied the evolution of H5N1 influenza viruses in Egypt by analyzing the sequences of 106 viruses isolated there from birds and humans between 2006 and 2009: 85 sequences were obtained from the National Center for Biotechnology Information (NCBI) database, and 21 sequences were newly obtained in this study. At the time of this investigation, these 106 sequences represented 40% of the complete and partial H5N1 virus sequences from Egypt in public databases.

Note, the authors used sequences from NCBI, *not* GISAID. The former is run by NIH, the latter by a ski instructor (really). I’m not sure if it is even permissible to state publicly how many Egyptian H5N1 sequences GISAID contains (due to the restrictions put on their use by the Ski Instructor), but whatever that number is, none of them were used in this analysis.

The authors found that the genetic diversity of the haemagglutinin (HA) protein of H5N1 in Egypt greatly increased in 2007-2008. This prompted them to perform binding assays to determine whether the virus had become better able to enter human cells. There are two general types of receptor for influenza viruses: α2,3 SA (associated with infection of birds) and α2,6 SA (associated with infection of humans). Some of the viruses they tested seemed to have an increased affinity to α2,6 SA and thus perhaps an increased ability to infect humans. Additional studies conducted by the authors support an increased ability of the newer Egyptian isolates to infect the human respiratory system.

One bit of good news was that the H5N1 viruses in Egypt did not bind well to cells in the larynx and only moderately well to cells in the trachea. Fully human adapted flu viruses bind well to both these tissues. The authors conclude that this may explain why the H5N1 viruses in Egypt are not yet able to cause sustained human to human transmission.

Unfortunately, there are many other H5N1 viruses, each with their own characteristics. It is possible that all of the elements necessary to create a highly infectious, highly lethal flu virus already exist in separate viruses. Since flu viruses can exchange genetic material quite easily, the emergence of a new flu virus with the worst possible characteristics could emerge at any time.

From the paper:

Since clade 2.2 appeared in Egypt in 2006, Egypt has had a single known introduction of a clade 2.2.1 H5N1 virus. Neither introduction of other phylogenetically distinct sublineages of clade 2.2 (I, II and III) nor reassortment events between the sublineages, as detected in neighboring Nigeria, have been documented in Egypt. Such events also were not observed in our phylogenetic analyses of HA and NA genes. However, introduction of these sublineages into Egypt could accelerate the evolutionary dynamics of H5N1 virus. Moreover, all Egyptian viruses (clade 2.2.1), which emerged during the 2005 Qinghai Lake outbreak in China, have mammalian-type PB2-627Lys, implying the potential for evolution to a pandemic virus. Therefore, there is a critical need for continued surveillance of birds to monitor receptor specificities of H5N1 field isolates in Egypt as well as the pandemic potential of these strains.

Reference

Watanabe, et al. (2011) Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt. PLoS Pathogens.

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