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Paradigm Shift Intervention Monitoring | Audio: Jan28 Apr21
Commentary Hoarding of Human H7N2 Sequences Creates Confusion Recombinomics Commentary 12:58 May 29, 2008 Additionally, the results of this study indicate that increased virus binding to 2–6 SA is not sufficient for transmission of avian influenza viruses to occur, supporting previous studies demonstrating the lack of transmission of an H5N1 virus with an increased 2–6-binding preference (21, 22). We identified a LPAI H7N2 virus, NY/107, which was associated with human respiratory infection and not ocular disease and was effectively transmitted in the ferret model by direct contact (10). Among all H7 viruses analyzed by glycan microarray, NY/107 displayed the most dramatic increase in 2–6 SA binding along with decreased 2–3 SA binding avidity. 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, The finding of enhanced 2–6 SA binding of North American H7 viruses underscores the necessity for continued surveillance and study of these viruses as they continue to resemble viruses with pandemic potential. The above comments from the discussion section of this week’s PNAS paper highlight some of the important biological aspects of the H7N2 isolated from a New York patient in 2003. The ferret to ferret transmission and receptor binding properties were the subject of a PNAS commentary as well as popular press articles. However, the removal of the underlying sequences of the virus, A/New York/107/2003(H7N2) has created confusion rergarding the interpretation of the animal studies, which were part of the PNAS paper and a Journal of Virology paper published last year. In both instances, the journals published the papers in the absence of deposited sequences in a public database. Peer reviewed journals require that papers include sufficient detail to allow for independent confirmation of the published results. However, neither paper includes accession numbers for access of the public sequences, and the sequences were not deposited at Genbank until March 24, 2008, three days after acceptance by PNAS. These sequences represented clear reassortment, with three avian genes (HA, NA, NP) and four human genes (PB1, PA, MP, NS). The PB2 sequence was not deposited. The sequences were publicly accessible a month ago, and have since been removed because the origin is uncertain. Thus, the reason for the enhanced transmission is unclear, because it is not clear if the human genes were in the isolates used in the mouse and ferret experiments, or if the human genes were in the original isolate from the patient infected 4 ½ years ago. This uncertainty highlights the dangers of sequence hoarding and the failure of the peer reviewed journals to require the deposit of sequences prior to publication. Although WHO has recently called for a paradigm shift on sharing influenza data, it still maintains a private sequence database accessible only by WHO consultants. This database gives license to WHO consultants to hoard data and seriously impede scientific understanding. WHO consultants are the most blatant sequence hoarders, in part because they are mailed samples from around the world, so avian influenza infections can be confirmed. These consultants then generate sequences data which they then “own” and hoard. Journals aid and abet this hoarding by allowing publication of data generated by isolates from these samples, without requiring deposit of the sequences. The H7N2 isolate represents the human / avian reassortant which has not been reported previously for H7N2 or H5N1. This reassortant has been the “holy grail” of the WHO consultants who repeated characterize H5N1 isolates as not having significant mutations because human genes are not found. In this case, if the human genes are not artifacts generated in the lab, WHO a consultant (CDC) has had a clear example since 2003, but hadn’t generated the sequence data, or failed to analyze the sequence data. The HA sequence was clearly generated over a year ago, because it was described in the Journal of Virology paper and used in the phylogenetic tree, which was Figure 1. The HA sequence was again described in detail in the PNAS paper. However, neither paper included accession numbers for the sequences, even though at least seven sequences had been completed near the time of acceptance and two months prior to publication. The presence of the human sequences was discussed a month ago, before they were removed from the Genabnk database. The question of origins was not included in any of the interviews on the paper published by the popular press this week. Similarly, there was no mention of the H7N2 outbreak in England a year ago, which also generated respiratory disease. Although there were more suspect human cases than confirmed poultry cases, the infections in most of the suspect cases was not confirmed. Moreover, the sequences from that outbreak are being hoarded by another WHO consultant and regional reference lab (Weybridge) . The sequence hoarding and oversight failures continue to be hazardous to the world’s health. Media Links Recombinomics Presentations Recombinomics Publications Recombinomics Paper at Nature Precedings |
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