Commentary
Curious Removal of Human H7N2 Reassortant Sequences
Recombinomics Commentary 12:40
May 28, 2008
Efficient contact transmission was also not observed with Tky/VA virus, despite this virus sharing 98.4% HA amino acid identity with NY/107 virus (40). Future studies will allow for a better understanding of the genetic determinants responsible for the heightened transmissibility observed with this virus. NY/107 virus, like all H7 viruses tested in this study, did not transmit by respiratory droplets in the ferret model. However, the efficient NY/107 virus transmission observed by direct contact in ferrets has not been observed with HPAI H5N1 viruses (21, 22) and may indicate the capacity of a NY/107-like virus to acquire properties that would confer efficient transmission by respiratory droplets; this underscores the importance of studying virus transmissibility by both routes.
LPAI H7N2 viruses have been acquiring additional basic amino acids at the HA cleavage site since 1994, resulting in a cleavage site that more closely resembles HPAI viruses (51). These viruses are also characterized by a deletion of 8 aa in the HA1 proximal to the receptor-binding site (31);
The above comments in this week's PNAS report describe the HA sequence from a patient in New York, A/New York/107/2003(H7N2). The comments are similar to descriptions in a Journal of Virology article from last year. Both journals are peer reviewed, which requires that the paper contain sufficient information for the observations and conclusions to be independently confirmed. Normally, papers that include descriptions of sequence data require deposit of the sequences in a public database, such as Genbank, and the first paper to discuss the sequences includes accession numbers.
However, sequences were not deposited in association of the J Virol paper, which was more focused on public H7 sequences from the H7N7 2003 outbreak. However, NY/207 was used in mouse and ferret models and demonstrated transmission of respiratory disease. In this week’s paper however, one of the main foci is the isolate from the H7N2 infected New York patient (infected in 2002 and diagnosed in 2003). This paper was accepted on March 21, 2008 and sequences from seven of the eight gene segments were deposited at Genbank three days later (March 24, 2008).
The deposited sequences represented an avian / human reassortant, with avian HA, NA and NP genes packaged with human H3N2 genes (PB1, PA, MP, NS). The human genes were closely related to human H3N2 sequences from patients infected in New York in 2002/2003, which would be the first avian / human H7N2 reassortant reported to date. These sequences were accessible to the public in late April and were the subject of three commentaries (here here here).
Shortly thereafter, the sequences were withdrawn, but can still be accessed at the above links for each gene.
The depositied HA sequence matches the descriptions quoted above, as well as descriptions in the J Virol paper. However, neither paper mentions accession numbers and the HA sequence was not available when the J Virol paper was published. The deposits on March 24 appear to be linked to the acceptance of the PNAS paper, but have since been labeled “This record was removed at the submitter's request because the source organism cannot be confirmed.”
The removal of the sequences is curious since the virus is required to do the experiments described in the J Virol and PNAS paper, and sequencing of an isolated virus only takes a few days. The H7N2 infection was confirmed over four years ago, so there would be ample time to sequence and re-sequence all eight gene segments from the isolated virus.
No data has been reported for the PB2 gene. In human influenza, the PB2 gene contains E627K, which allows the virus to optimally replicate ate at lower temperatures (33 C) and has been associated with increased H5N1 virulence in mice. The only avian influenza reported to cause a human fatality, other than H5N1, was an H7N7 infection in the Netherlands in 2003. That isolate had E627K.
Thus, the sequences of the H7N2 from the patient in New York are directly related to the PNAS paper, yet the paper has no accession numbers or mention of the fact that the public sequence data has been removed.
A detailed explanation would be useful.
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