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Japan's H5N2 Wild Bird Flu From North and Central America

Recombinomics Commentary

September 4, 2005
Artificial infection, including the use of vaccines, could be behind a weak strain of avian influenza detected in poultry farms in Japan's Ibaraki Prefecture, according to a panel advising the agriculture ministry on bird flu. Unauthorized vaccines could have been used……….

The virus was detected in chickens at seven of the farms.

An analysis by the National Institute of Animal Health, an independent administrative corporation, found that the genetic makeup of the virus bore a strong similarity to a virus found in Central and South American countries, including Mexico and Guatemala. The virus did not exist in Japan, and it is highly unlikely it was carried to the country by migratory birds…..

A prefectural government official said that so far, no indications pointing to the use of vaccines had been found.

Several owners of poultry farms where the virus has been detected said they did not use vaccines, including those from overseas.

The above comments on the likelihood of H5N2 transmission to Asia by migratory are curious.  H5N2 has been recently detected in Taiwan,
A/chicken/Taiwan/1209/03(H5N2), and South Korea.  In both instances the H5N2 isolated was related to H5N2 from the Americas.

The H5N1 explosion in Asia was almost certainly initiated by sequences brought into the area by migratory birds.  The sequences appeared in Hong Kong in 2002 and 2003 as recombinants.  The pandemic followed the next year.

The initial reported H5 outbreak was at the end of 2003 in Taiwan.  The sequences of the H and N are available, and the virus is most closely related to H5N2 from Mexico.  However, the isolate also has polymorphisms linked to Asia, including at least one that was subsequently found in H5N1 infected patients in Vietnam.

Similarly, the cleavage site of H5N2 isolated from South Korea at the beginning of this year is most closely related to cleavage sites fro H5N2 from the America.

In both of the above instances, the H5N2 was LPAI.  Although Japan has not made sequence data available, their OIE reports characterize the H5N2 as LPAI, and the comments above indicate that the sequences are similar to the Taiwan sequence.

Since H5N2 viral sequences have been found in all three countries, vaccines are an unlikely source.  Although the vaccine could generate H5 antibodies, the vaccines would not likely have live virus.  The published cleavage sites from Taiwan and South Korea are similar, but distinct.  The South Korea sequence is unique, while Taiwan matched an H5N3 isolated from Texas

Since the Taiwan sequence has already picked up Asian polymorphisms, it appears to be replicating.  These sequences offer an opportunity to recombine with H5N1 sequences.  H5N1 from Qinghai Lake has many H5N2 polymorphisms from Europe, even though the genetic background, including the HA cleave site is clearly from H5N1 HPIA from Asia.

The finding of one of the Taiwan polymorphisms in H5N1 from three patients in Vietnam (
A/Hanoi/03/2004, A/Viet Nam/3046/2004 ,  A/Vietnam/3212/2004 ) demonstrates how LPAI sequences can end up in HPAI H5N1.

Many recent comments on H5N1 wild bird flu have demonstrated a fundamental misunderstanding of how H5N1 emerges and evolves.  Wild birds transport sequences that may be from LPAI isolates such as H9N2 and H5N2, but these sequences are incorporated into H5N1, as are mammalian sequences.

The H5N1 wild bird flu has led to increased monitoring.  Isolation of influenza A from wild birds will expand the sequence database and more clearly demonstration recombination and evolution of H5N1 via acquisition of the polymorphisms carried by migratory birds.

The aquisition of these polymorphims plays a fundamental role in the evolution and pathogenesis of H5N1


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