Commentary
H7N2 New York Case Due to Human Transmission?
Recombinomics Commentary 20:41
May 29, 2008
Researchers have found that some North American strains of influenza have increased their affinity for human cell surface molecules. These findings suggest that the viruses are coming closer to attaining the characteristics needed to cause a human pandemic and that surveillance of avian flu viruses, and preparations for a possible pandemic, should continue.
They show that one strain of the H7N2 virus, isolated from a man in New York in 2003, replicated in the ferret respiratory tract and was capable of transmission through direct contact with other ferrets. Belser et al. suggest that these viruses could be evolving toward the same strong, sugar-binding properties that characterized the three pandemic viruses of the 20th century. If this evolution continues, avian flu viruses could potentially travel easily between animals and humans, according to the authors.
The above description from the PNAS commentary highlights the importance of the H7N2 isolate, A/New York/107/2003(H7N2). However, interpretation of the experimental results is muddied with the removal of the sequences from the public database shortly after they became public in late April. The deposited sequences clearly represented reassortment data since three of the sequences (H7, N2, NP) were avian, and the other four sequences were human (PB1, PA, MP, NS). The sequence of the eighth gene segment (PB2) was not made publc. The removal of the sequences by the submitter, because the origin of the sequences could not be determined, raises concerns that the sequences are due to lab artifact or a dual infection.
However, there is significant support for reassortment. The human sequences are closely related to H3N2 isolates from New York isolated in 2003, which is the expected result if the H7N2 was an early lab artifact, or was due to a dual infection. The patient was initially thought to be H1N1 infected, strongly suggesting that he tested negative for H3N2. If the original infection was a dual infection, the patient should have been positive for H3N2. If the virus was a reassortant, the patient would not have tested positive for either seasonal flu serotype, because both HA and NA were avian.
If the H7N2 in the patient matched the removed sequences, then the isolate would be a major discovery, because a reassortant between human and avian H5N1 or H7N2 genes has not been reported previously. Experiments which created reassortants with human H3N2 and H5N1 were viable, but generally did not replicate or transmit as efficiently as viruses with only avian genes. In this case however, the reassortant was transmitted more efficiently from ferret to ferret and had increase binding for human receptors, and decreased binding for avian receptors. Moreover, the infection in 2002 was not linked to any poultry exposure.
If the virus was a human / avian reassortant and the patient was not co-infected with H3N2, then it is likely that he was infected by another human, since the H7N2 had human genes. These data would raise concerns of undetected H7N2 transmissions.
Thus, the delay and/or hoarding of sequence data has clouded the interpretation of the animal experiments, as well as considerations of human to human transmissions. This delay in the human case in New York is compounded by delays in release of sequence data from human cases in England linked to the H7N2 outbreak there a year ago. These sequences are being hoarded by another WHO regional center.
The continued widespread hoarding of sequence data by WHO regional labs continues to be hazardous to the world’s health.
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