225E with Adjacent 226R on Novgorod01 May Signal Instability and Hyper-morphic Behaviour at the Receptor Binding Domain

On 2009-12-30, Russia's Vector labs deposited a novel sequence with dual adjacent HA RBD changes as part of a signal-dense batch of data from 4 additional samples.  All are compelling because each shows a polymorphism at position 225, but A/Novgorod/01/2009 is special and may herald a new phase of maturation within ΣPF11.

Special sequence and special location.  Let's talk about geographic connectedness, location, for one moment before examining the sequence.

Though we cannot be certain which Novgorod is the sample location, we will profile one of the two for connectedness in this initial evaluation.  Nizhny Novgorod, in general, was founded at the confluence of the Volga and Oka rivers and is Russia's fourth largest city with a population of 1.3 million.  The geographic and economic details discussed here are supplied by the Nizhny Novgorod entry from Wikipedia.  This city, that you may recall as "Gorky" (1932-1990), offered an ideal administrative seat for the surrounding oblast.  The Kremlin was built in Nizhny Novgorod between 1508 and 1511. 

Though the area is well-connected via multiple transport hubs including the Trans-Siberian Railway, the city was closed to foreign tourism for most of the Soviet era due to military research and development.  Today direct trains run to many Russian cities and to Beijing.  Airports serve Frankfurt, Germany 3 times per week.  The Ukraine, Belarus and Kazakhstan feature in the top four of import and of export partners for this area.  Additional to the extensive cargo transport, passenger cruise vessels operate on the Volga from this area to various Russian cities including Astrakhan where H5N1 has been active in wild birds and humans.

Information about Veliky Novgorod (Great Novgorod) is also available at Wikipedia.

With those transmission vectors, ingres and egress in mind, let's examine the sequence sampled in Novgorod.

Novgorod01 appears to be the first human sequence in this pandemic to carry the dual adjacent RBD polymorphisms of 225E with 226R.  Though we may expect at some point to see 225G paired with 226R, this 225E+226R combination from Russia is yet another point of data to use in determining randomisation versus patterning.  We personally begin to speculate and revise our opinion that the expressively variant RBD sequences recently from Singapore may perhaps be perfectly valid and not the result of lab error?

Though the analysis is far from complete on this set of lung samples from Russia, a second point of interest does come to the forefront.  Preliminary review shows that A/Abakan/02/2009 demonstrates a mixture at HA amino acid position 246 coding for an alternate 246S, a polymorphism found once in the present pandemic with Auckland04, but more importantly found in sequences of H2N2 (Asian Flu Pandemic of 1957) and H2N8 (Asiatic Flu Pandemic of 1889-1890).  Abakan sits near a very large body of water (Krasnoyarskoye) and is somewhat centered north of Mongolia and east of Kazakhstan, geographically providing a mixing area for wild birds.

Of course, we would be remiss to fail mentioning that 225G is found in 3 of the 5 Vector isolates with 225E in the other 2.

This first reported instance (Novgorod01) of adjacent Receptor Binding Site amino acids on one sequence, 225E plus 226R, may equate to a direction change in ΣPF11 signalling a more persistent hyper-morphic behaviour in the reservoir.  At any rate, the recent reports from Russia demonstrate a geographically widespread incursion of polymorphism at amino acid 225, including 225E, 225N (Orenburg) and 225G, presumably on fatal cases. 

Will we also see 225S emerge in Russia or the surrounding states? 

Is ΣPF11 learning how to become a more deadly pandemic virus from previous pandemics of differing serotypes?  Is the ecosystem of Influenza reservoirs more promiscuous than our level of surveillance (granularity and geography) has led us to believe?

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