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Withheld H5N2 Fraser Valley Sequences Raise Concerns
Recombinomics Commentary
December 11, 2014 13:00

partial sequencing of the H and N gene segments indicates a poly-basic cleavage site in H5 consistent with Highly Pathogenic Avian Influenza Virus and the virus being a H5N2 Avian Influenza Virus with an IVPI of 2.96-2.98

The initial testing was done after turkeys on a 50,000 bird farm showed signs of respiratory distress.
If the Winnipeg lab confirms the presence of H5 viruses, additional tests will be needed to identify the virus's neuraminidase subtype – the N in a flu virus's name – and whether the virus is of high or low pathogenicity.
Low path viruses, as they are called, typically only lead to a drop in egg production. But high path viruses are dreaded in poultry operations because they can wipe out whole flocks. And the birds that don't die must be culled to extinguish the outbreak.
In 2004, 17 million birds died or were destroyed in an outbreak caused by a high path H7N3 virus in the Fraser Valley.
Mazur said it would be a couple of days before the full specifics of the virus type would be known.
The presence of H5 virus, if it is confirmed, does not mean there is an outbreak of the H5N1 virus that has killed nearly 250 people in parts of Asia, Africa and Europe. There are multiple subtypes of H5 avian flu. In fact, the Fraser Valley experienced an H5N2 outbreak in November 2005.
Even within H5N1 viruses there are different lineages or families of viruses. The one which has wrecked such havoc in Asia and parts of Africa has so far not been found in North America.
"We have no evidence that it's the Eurasian lineage (virus)," said influenza expert Dr. Danuta Skowronski of the British Columbia Centre for Disease Control.
"And given what's been found previously in North America, it's most likely the North American lineage."

The above comments (in red) are from the CFIA December 9 OIE report, which notes that the current avian influenza outbreak in Fraser Valley is high path and the report indicates that the national lab in Winnipeg successfully isolated the virus and obtained a sequence on December 4.  The sequence would have included the polybasic cleavage site, but the above comments do not include the actual sequence and the lineage is glaringly absent.

The report does give the intravenous pathogenicity index (IVIP) which is a biological test which experimentally infects 10 chickens and then monitors the health of each chicken with a score between 0 (asymptomatic) and 3 (death) for 10 days.  The 100 scores are then divided by 100 to obtain a score between 0.00-3.00 (a score of 0 would indicate all 10 chickens remained asymptomatic for 10 days, while a score of 3.00 would mean that all 10 chickens died within 24 hours of infection).  A value of 1.2 or higher defines highly pathogenic avian influenza (HPAI).  The above value of 2.96-2.98 is higher than most tests for Asian high path H5N1, and the value indicates almost all of the chickens died within 24 hours of infection.

Thus, the very high IVIP strongly suggests that the infection is due to an Asian HPAI H5, and the absence of the sequence or lineage in the OIE report is glaring and violates the UN’s Internal Health Regulations (IHRs), which require notification within 24 hours of lab results (on December 4).

The above comments (in blue) are from a 2009 media report which details the differences between serotypes and lineages and suggests the H5 will be low path and have a North American lineage, which was subsequently confirmed.

Canada has had three H5 outbreaks since 2005 and all three were H5N2 and were low path sequences of a North American lineage, which the CFIA quickly noted.  For the November, 2095 outbreak in Fraser Valley, the CFIA deposited the H5 and N2 sequences, A/duck/BritishColumbia/CN26-6/05, at Genbank that same month (which had a cleavage site of RETR).  For the 2009 outbreak in Fraser Valley described above (which is the same turkey farm in Aldergrove, which is designated as sites 5 and 6 in the current outbreak - see map) the OIE report included the sequence for the cleavage site, which was also RETR, and noted that the sequences reflected a North American lineage.  Similarly, the OIE report for the 2010 H5N2 outbreak in Manitoba was low path and a North American lineage, and full sequences from two turkeys (A/turkey/MB/FAV10/2010 and A/turkey/MB/FAV11/2010) where subsequently published with the same low path cleavage site of RETR and sequences which were of North American lineage for all 8 gene segments.

In contrast,  media reports suggest the current H5N2 outbreak is similar to the prior three H5N2 low path outbreaks, that involves a similar virus which has evolved from low path to high path as has happened previously in Canada for H7N3, which included the 2004 outbreak in Fraser Valley that result in the death of 16-17 million birds.

However, CFIA has not provided any data supporting a North American lineage for the current outbreak, and has withheld the cleavage site sequences, as well as the additional sequence data for H5 and N2 (and sequences for all 8 gene segments, which it undoubtedly has).
Sequences would show if the H5 is of Asian lineage. 

Fujian H5 clade 2.3.4 is widespread in Asia and is circulating in multiple serotypes, including H5N1, H5N2, H5N5, H5N6, and H5N8.  These sero-types largely have two closely related polybasic cleave sites (RERRRKR or REKRRKR) which substitute four basic amino acids for the T present in the low path cleavage site (RETR).  The presence of either of the Fujian polybasic cleavage sites would signal an Asian lineage for the H5, and sequencing of the other 7 gene segments would determine which also have an Asian lineage.

Mixtures between Asia and North America were seen in pandemic H1N1, which had 2 Eurasian genes (N1 and MP) in association with North American lineages for the other 6 gene segments (H1, PB2, PB1, PA, NP, NS).

The presence of one of more Asian gene segments in H5N2 would signal infections by wild birds and would raise serious health concerns because of fatal human infections in China involving Fujian clade 2.3.4 H5 as well as the migration of wild birds to countries south of Canada, including the US, which is 2 miles from the two sites in Aldergrove.

Sequences for all 8 gene segments should be released immediately.

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