A Tail of Three Cities Brings Novelty to Nanjing

Nanjing, a city just inland and slightly northwest of Shanghai, is the tail in a trail of recombinations.

A/Nanjing3, sampled on 2009-10-17, displays a pair of distinctive polymorphisms on the HA and NA that were only previously found at Chengdu on multiple sequences from a cluster in the summer and then on one sequence, Hangzhou2, from September (also inland and adjacent to Shanghai). 

131P on the HA is carried across all three cities and is unique to this set of sequences studied here.  As no Hangzhou neuraminidase was published, the NA trail has only the origin city of Chengdu and the tail of Nanjing.  All 13 Chengdu NA segments and Nanjing3 display a NA revision not found elsewhere in this pandemic reservoir.  A silent SNP at the third base codon, A945G, sets this sequence as novel within ΣPF11, revising “GGa -> GGg” and coding for a synonymous Glycine at residue 315 (syn315G). The A945G SNP appears at GenBank within 2 earlier H1N1 Swine samples,  A/swine/Ratchaburi/NIAH550/2003 and A/swine/England/WVL16/1998.

Paired changes crossing both antigen segments (HA, NA) traveling sequentially between three cities potentially via human transmission is a nice story, but not entirely compelling.  Nanjing3 also carries additional genetic informational changes on the HA and the NA that are found on previously identified donor candidates.  Fidelity to the origin strain in one area and acquisition in another area on each antigenic segment is the tale of this tail.

The HA demonstrates a silent SNP at the third base codon, G1587A, revising “CAg -> CAa” and coding for a synonymous Glutamine at residue 515 (syn515Q). The G1587A SNP appears at GenBank extensively within US H1N1 Swine samples, including A/swine/Illinois/Sg-00445/2008 and two others in the series, Sg-00443 & Sg-00444.   The only sample found in Asia is an H1N2 2006, A/swine/Hong Kong/1110/2006.

The Neuraminidase carries several changes, syn8I, 199G, syn307N, syn315G (previously discussed).  The first is a silent SNP at the third base codon, A24C, revising “ATa -> ATc” and coding for a synonymous Isoleucine at residue 8 (syn8I). The A24C SNP appears at GenBank only on one H6N1 Avian sequence, A/chukkar/Shantou/3182/2004.   The second silent SNP, also at the 3rd base, C921T, revising “AAc -> AAt” and coding for a synonymous Asparagine at residue 307 (syn307N) features extensively in H1N1 Swine and H6N1 Avian at GenBank including the special partridge carrying the A24C, A/chukkar/Shantou/3182/2004.  One H1N1 Avian mallard from 1983 also carries the C921T.

The data along this FlightPath suggests anything other than re-assortment and random mutation as explanations for these genetic acquisitions.  Fidelity at HA 131P and the NA syn315G while acquiring a Swine H1N1 SNP on the HA and 2 H6N1 Avian SNPs on the NA is highly suggestive of dual and potentially triple infection resulting in Influenza Flux.  No sloppy polymerase at work here . . . just a reservoir recycling revisions to reach an optimal environmental match.

Did a child from the boarding school with a latent PF11 infection travel eastward to Hangzhou on break in September and visit an older sister, 21F, who later returned to college or work in Nanjing?  Where will the Chengdu strains extend their range next?

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