Thursday, February 23, 2012

Recombinomics Commentary: Similarities In CDC and Fouchier H5N1 Transmission Papers

February 23, 2012


A reverse genetics virus with HA of EG06-196R/226L/228S, the N2 neuraminidase from a human seasonal H3N2 virus, A/Brisbane/10/2007, and 6 internal genes from a clade 1 H5N1 virus, VN04, known to replicate efficiently in ferrets (Maines et al., 2011), was generated and evaluated in the ferret transmission model. As shown in Table 2, both direct contact ferrets that were housed in the same cage with inoculated ferrets became infected, as evidenced by virus shedding and seroconversion results. In addition, viral shedding was also detected in one of two ferrets housed in adjacent cages and exposed only via respiratory droplets.

The above comments are from the CDC paper, “In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity", published online on November 5, 2011 in the journal Virology. As noted above, the three receptor binding domain changes included the two most noted changes in H5N1 transmission discussions, Q226L and G228S, along with Q196R which was present in H5N1 clusters in Iraq and described in previous studies by Kawaoa. These changes were placed on a clade 2.2 H5 (A/egret/Egypt/1162/2006) which was pl aced on a genetic background using human N2 (A/Brisbane/10/2007) 6 H5N1 clade 1 genes (A/Vietnam/1203/2004), which includes PB2 E627K. This combination led to H5N1 transmission in ferrets via respiratory droplets as stated above.
... but it is well known that H1N1pdm09 PB2 can substitute for H5N1 PB2 with E627K to produce efficient human transmission, and H1N1pdm09 is widespread in humans, swine, and turkeys which provide natural opportunities for the creation of an H5 reassortant with a composition that matches the H5N1 used by Kawaoka in his paper in Nature.

Click on Title for full Commentary

No comments: