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H2N2 Pandemic Flu Labeling Errors Remain Murky

Recombinomics Commentary

April 14, 2005

>>  Dr. Jared Schwartz, an officer with the pathologists college, said Meridian thought it had sent an ordinary flu strain. He said Meridian workers found a virus in their "germ library" from the year 2000, which they'd gotten from another company which had obtained it from yet another company.

According to Meridian's process and evaluation they thought it was "an innocuous, typical influenza A virus, the kind of virus they've used before in our programs," Schwartz said.

Meridian executives were traveling and not available to comment, spokeswoman Brenda Hughes said.

Dr. Julie Gerberding, head of the Centers for Disease Control and Prevention, said labs doing proficiency tests generally only identify whether a flu virus is in the sample and whether it is a type A or B - not further sub-typing.

"That's why we didn't learn about this earlier in the process," she said.

So the deadly strain was in many labs for months before one lab discovered that the sample was the deadly H2N2 Asian flu virus from the 1957 pandemic.  <<

The above description indicates that the 1957 H2N2 pandemic virus was mislabeled at some point between 1957 and 2004.  This created confusion about the origins of the virus shipped out since last fall as part of a lab proficiency test.  The recording error is supported by the paperwork associated with the shipments, which indicated the virus was H3N2.  Since H2N2 was virtually eliminated from circulation in humans in 1968, it should not be in a library of viruses from 2000.

Clearly the virus in the proficiency test was the H2N2 pandemic strain and destroying those samples should be relatively easy because they would be part of a well labeled and tracked kit.  However, finding and destroying or relabeling the pandemic strain that was mislabeled originally will be a challenge.  Reclassifying the virus will not help, because it appears to be currently labeled as something else with an H3N2 serotype from 2000.  Viruses in that category are relatively benign.  In contrast the H2N2 pandemic strain is quite transmissible in humans and those born after 1968 would have limited immunity.

There is widespread agreement that the virus in the kits should be destroyed and the mislabeled virus should be destroyed or properly labeled.

This situation has some obvious parallels with the controversy regarding the WSN/33 sequences reported to be in isolates from pigs in Korea in 2004.  Like the pandemic 1957 strain, WSN/33 has been out of circulation in humans for a long period. It was the first human influenza virus isolated, which happened in 1933.  WSN/33 is a lab strain that was developed by infecting mice with the virus in 1940, and isolating WSN/33 from brain tissue. 

Consequently the virus is lethal in mice and is neurotropic.  During the selection process it lost a glycosylation site, which allowed the virus to sequester plasminogen.  This facilitated cleavage of the HA protein and allowed the virus to grow under a wide range of conditions, including cells in culture.  It became a popular lab virus, just as the 1957 virus was popular because it grew so well in the lab.

Thus, like 1957 H2N2, 1933 H1N1 WSN/33 is a lab virus that could cause significant problems if it infected a person born after 1933.  It could cause problems in just about any person, because it had also been selected for its ability to grow in mouse brains.  It is also resistant to the antiviral drugs Amantadine and Rimantadine. 

When WHO was notified of the WSN/33 sequences in swine isolates they exchanged e-mails with consultants and concluded that the sequences at GenBank were likely generated by a lab error.  Therefore, the virus from the swine did not actually contain WSN/33 genes.  This conclusion was based in part because one of the consultants had indicated that his lab had sent WSN/33 to the lab in Korea.  However, the lab in Korea insisted that a different virus was received.  Moreover, the isolates from the pigs were grown in chicken eggs, not cell lines, further reducing the likelihood that WSN/33 could have contaminated the swine samples.

Consequently WHO launched a more intensive investigation to confirm or refute the WSN/33 genes in the pigs.  The investigation should have been quite straightforward.  If WSN/33 genes were in the pigs, they should have been able to sequence the viruses and confirm the data at GenBank, which showed that six isolates were part WSN/33 and part avian H9N2 from Korea.  If the WSN/33 had somehow contaminated the samples, then they should be able to find virus in the swine that had eight avian H9N2 genes.

Remarkably, after 5 months, WHO has not been able to prove or refute the data at GenBank.  Moreover, they have elected to stop trying.  Thus, if the data is correct, the virus is circulating in pigs and there is no explanation on how the virus moved from a lab to many pigs on many pig farms in Korea. If the data is incorrect, then how the data was generated will remain unknown, and there will be no full data set on the H9N2 genes.  WHO has indicated that they will continue to look for the H9N2, but consider the WSN/33 sequences to be due to lab error.

In view of the consequences of WSN/33 circulating in humans, it would seem that WHO should conduct its future efforts with more urgency, rather than treating important research as a curiosity.

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