Commentary
Unclear Origins of Human H7N2 Sequences from New York
Recombinomics Commentary 23:56
May 28, 2008
Jessica Belser et al. analyzed the binding strength between several recent avian flu viruses and the sialic acid sugar molecules found on the surface of human and ferret cells. The authors found that a few of the H7 strains that caused minor, untransmissible viral infections in individuals in North America between 2002 and 2004 have increased their affinity for the sialic acids found on human tracheal cells. 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 comments by PNAS highlight the potential importance of A/New York.107/2003(H7N2) isolated from a patient in New York who presented in November, 2002. This paper was accepted for publication on March 21, 2008, and sequences from seven of the eight gene segments were deposited at Genbank on March 24, 2008. These sequences became public a month later. Three of the sequences (HA, NA, NP), were avian H7N2, while four of the sequences (PB1, PA, MP, NS) were human H3N2 (most closely related to New York sequences circa 2003). The sequence data clearly indicated the virus was an avian / human reassortant. However, the characterization sheets were entitled “A Human Case of Influenza A (H7N2) in New York State, 2003” and made no mention of the reassorted nature of the sequences, which had never been previously reported for H7N2.
A year earlier the isolate was used in a Journal of Virology paper, “Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans” and although the sequence of the HA was used in the HA1 phylogenetic tree, there was no mention of human gene sequences. Similarly, this week’s PNAS paper also describes the sequence of HA, but also does not mention the human genes.
The lack of any discussion of human sequences in either paper suggests the sequences of the human genes had not been generated or analyzed prior to the publication of these two papers.
The removal of the sequences from Genbank within a month of release suggests that the validity of the human sequences is uncertain. If the human sequences are due to lab generation of the reassortants via contamination, then the previously described results from the mouse ands ferret studies would not be applicable to the H7N2 isolated from the patient. However, the human sequences are most closely related to sequences from New York isolated in 2003, suggesting that the reassortant was naturally formed in the patient or another patient in the area around the time of infection in 2002.
The removal of the sequences suggests the origin of the sequences is uncertain.
More information on the history of these sequences as well as the sequence of PB2, would be useful.
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