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Commentary
H7N9 Avian
Swine Human Adaptation
Recombinomics
Commentary 20:30
April 4, 2013
The above translation of a tweet suggesting an explanation for the large number of dead swine floating through Shanghai and subsequent explosion of human H7N9 cases in the same general area is of interest
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The H7N9 sequences released by the WHO Chinese Influenza Center (at GISAID) over the weekend were from the first three confirmed cases. All were closely related and had H7 and N9 wrapped around six H9N2 internal genes. H9N2 is the most common serotype in wild birds in China and there are significant interactions between wild birds and domestic poultry. The above tweet also provides a mechanism for interactions between poultry and swine, and acquired polymorphisms in internal genes are seen between H9N2 and H5N1, supporting avian influenza evolution.
The H7 in the three cases was low path, while the N9 had a 5 amino acid deletion in the stalk region, which could signal silent spread in poultry. However, the passage of this sequence in swine could lead to significant mammalian adaptation. All three PB2 sequences had E627K, which allows the polymerase to function optimally at 33 C, which is closer to a mammalian body temperature, than a polymerase with 627E, which operates optimally at 40C, the body temperature of a bird.
E627K leads to a more lethal virus in mammals, which could have produced the massive die-off and subsequent floating swine. The passage through swine may have led to a subsequent mammalian adaptation to produce the H7N9 sequence from the first confirmed case, A/Shanghai/1/2013, which was linked to two symptomatic sons. These cases were from the Minhang District, which was also the location for the second confirmed cases (A/Shanghai/2/2013) as well as a number of additional cases reported by local media (see map).
The Minhang District is adjacent to the Songiang District, where an H7N9 pigeon was identified with a sequence closely related to the human cases.
However, the human sequence acquired Q226L, signaling human adaptation, and Q226L was also in the third confirmed case (A/Anhui/1/2013), which was followed by the explosion of human cases.
The large number of human cases raises concerns of additional human adaptation leading to additional receptor binding domain changes. The sequences already have D225G and M230I, and addition of G228S may be catastrophic.
The April 4 WHO update confirms four additional cases (three fatal and one critical), signaling the severity seen in most confirmed cases.
More information on the sequences of these recent cases, as well as the H7N9 pigeon, would be useful.
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