Commentary
Frequency of Human H7N2 Infections Remains Cloudy
Recombinomics Commentary 19:29
May 28, 2008
Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.
Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.
Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.
The above comments summarize some of the recent data on A/New York/107/2003(H7N2), which was recently characterized in two journal articles, one in Journal of Virology last year, and one in the Proceedings of the National Academy of Sciences this week. Both articles highlight the H7N2 isolate because of its association with respiratory disease in mouse and ferret models, as well as changes in affinity for human flu receptors. The ability to cause and transmit respiratory disease in mammals is of concern, because avian viruses generally do not cause such diseases in humans. Other H7 isolates caused eye disease in humans and the two animal models, and are not as concerning because the eye disease is mild, although tests for H7 antibodies in contacts indicate the H7 is easily transmitted.
The validity of the lab data has come under question because the sequences from the New York isolate were deposited at Genbank three days after the acceptance of the PNAS paper, but then removed shortly thereafter. The deposited sequences represented 3 avian (H7, N2, NP) and four human gene segments (PB1, PA, NS, MP). The sequence of PB2 was not included. It remains unclear why the sequences were removed from the database. The sequences can be accessed, but have a red banner stating, “This record was removed at the submitter's request because the source organism cannot be confirmed.” This has led to confusion regarding the virus used in the published papers. If the virus was a lab artifact which had picked up human genes, then the papers would not be characterizing H7N2 from the patient, but rather a theoretical H7N2 that could form at some future date. However, the human sequences were H3N2 circa 2003 from New York, so they may in fact be real, raising questions on why the sequences were removed. The PNAS paper makes no reference to the deposited sequences, which is also confusing since the sequences were discussed in the manuscript and therefore should have been made public.
If the sequences are real, then this is the first H7N2 human / avian reassortant, which raises teh question of what the level of such infections exist in the general population. H7N2 infections are difficult to confirm as was seen in the H7N2 outbreak in England, where there were more suspect human cases than bird cases. Although these patients did not develop pneumonia, several were hospitalized for extended stays, and the large number of suspect cases raises concerns that the H7N2 was easily transmitted. Unlike earlier H7N7 and H7N3 infections, the infections in England, like the New York case, caused respiratory diseases. This outbreak was presented at the Options VI meeting in Toronto at the “breaker” session in June. The report raised concerns that the number of people and sites involved were larger than initial media reports and promised quick answers. However, quick answers were not forthcoming, and the final report described a minimal number of confirmed cases and did not answer questions about the suspect cases who had contact with the infected birds and developed flu symptoms in late May, early June where there were few seasonal flu cases in England.
Thus, there are still many unanswered questions. The removal of the H7N2 sequences from Genbank raises questions about the published research. If the removed sequences are real, then infections by human / avian isolates raise serious pandemic concerns, due in part to the ease of transmission. Moreover, the removed H7N2 sequences also raise questions about the relationship to H7N2 sequences in England, which also have not been made public.
The confusion regarding these sequences and England’s failure to release the H7N2 sequences from the late spring 2007 outbreak remain causes for concern.
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