Glycosylation on Position 240 In H5N1 Ferret Transmission



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H1N1 Consulting Paradigm Shift Viral Evolution Intervention Monitoring Vaccine Screening Vaccine Development Expression Profiling Drug Discovery Custom Therapies Patents	Audio:Jan18 Feb16 Mar15 Apr19 twitter Commentary Glycosylation on Position 240 In H5N1 Ferret Transmission Recombinomics Commentary 23:50 May 16, 2012 To determine whether additional mutations occurred in the HA of HA(N158D/N224K/Q226L)/CA04 during transmission, viral RNA was analysed from nasal washes of inoculated and contact ferrets (Fig. 4 and Supplementary Table 4). On day 5 after infection, the A242S and T318I mutations in HA were present in five (pairs 1, 3, 4, 5 and 6) and one (pair 2) of the six inoculated animals, respectively. Viruses derived from the contact animals of pair 1 on day 7 after contact had two changes in HA (K193N and A242S) (Fig. 1a), whereas those derived from the contact animals of pair 2 contained a single change in HA (T318I) (Fig. 1b), indicating that additional changes in HA occurred during the infection of ferrets with HA(N158D/N224K/Q226L)/CA04. No mutations in the remaining genes were detected in any of these viruses from nasal washes compared with the CA04 virus sequences. The recent H5N1 transmission paper in Nature has focused on the two changes acquired during passage in ferrets. The first change, N158D, abolished the glycosylation site in the H5 used by the Kawaoka study (which is also present in the H5 used in the Fouchier study, which has not yet been published in Science). Further passage of sequences which had N158D led to additional changes in H5 isolated from nasal washes, and most summaries have focused on the subsequent change, T318I, which was in a high titer collection (and T318I stabilized the virus). However, as cited above, 5 of the 6 ferrets had another change, A242S, which created a glycosylation site on the N at position 240. Moreover, ferrets infected with H5 containing N158D and T318I developed another change, A242T, (as seen in supplement table 5), which again created a gylycosylation site on the N at position 240. Thus, this change of A240S/T (which produces glycosylation at position 240) appears to be critical for ferret transmission via the constructs used in the Nature study. A242T is common in clade 2.2.1 F in Egypt, while N158D is common in clade 2.2.1 G in Egypt. The co-circulation of these two sub-clades with key changes leading to the creation and abolition of glycosylation sites increases pandemic concerns. Media Link Recombinomics Presentations Recombinomics Publications Recombinomics Paper at Nature Precedings

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