Endringer i pandemisk H1N1 i Norge samme som i Ukraina

New York Times skriver i dag at viruset som til nå er påvist i tre pasienter i Norge har den samme endringen (D225G) som er påvist i prøver fra Ukraina som ble offentliggjort i forgårs. (Oppdatering 24/11/09: norske sekvenser offentliggjort så langt påviser seks tilfeller av endringer i posisjon 225 slik som i Ukraina. En av disse har D225G, fem andre har D225E. Se bunnen av bloggposten for detaljer.) Både norske helsemyndigheter og Verdens helseorganisasjon har vært tilbakeholdne med informasjon og ikke opplyst om viruset som er påvist i Norge har samme genetiske endring som i Ukraina. New York Times er første store nyhetsmedium som melder at viruset som er påvist i Norge har D225G. "Norway reported finding a mutated virus in three people who died or were severely ill. The mutation, known as D222G on the receptor binding domain, allow the virus to grow deeper in the lungs. The mutation does not appear to be circulating and may have spontaneously arisen in the three patients, said Geir Stene-Larsen, director of the Norwegian Institute of Public Health. Only 3 of Norway’s 70 tested samples had it. Asked about that, Dr. Schuchat said the same mutation had also been found in mild cases in several countries, and it did not make the virus resistant to vaccine or to treatment with drugs like Tamiflu. She said that she did not want to “underplay” it, but that “it’s too soon to say what this will mean long term.” The D222G mutation allows the virus to bind to receptors on cells lining the lungs, which are slightly different from those in the nose and throat. Henry L. Niman, a flu tracker in Pittsburgh, has been warning for a week that D225G — the same mutation under a different numbering system — has been repeatedly found in Ukraine, which is in the grips of a severe outbreak and where surprising numbers of people have died with lung hemorrhages." Kilder: New York Times, recombinomics.com ----- "The mutation is being widely reported to be D222G (this is H1 numbering; it is 225 in H3 numbering). What this designation means is that in the spikes of hemagglutinin protein on the outside of the virus (parts of which elicit the primary immune response), the amino acid 222 places in from one end has changed from "D" (aspartate) to "G" (glycine)." Trying to understand the Norwegian swine flu mutations "1918 RBD D225G in Lung Cases in Ukraine and Norway Recombinomics Commentary 11:29 November 21, 2009 For the two 1918 HA variants, the South Carolina (SC) HA (with Asp190, Asp225) bound exclusively alpha2-6 receptors, while the New York (NY) variant, which differed only by one residue (Gly225), had mixed alpha2-6/alpha2-3 specificity, especially for sulfated oligosaccharides. The above description is from a paper analyzing receptor binding domain differences in sequences from the 1918 pandemic. The New York variant had D225G, the same change found in lung tissues from fatal swine H1N1 sequences in Brazil, Ukraine, and Norway. The above result clearly demonstrated a change in receptor specificity for D225G, which was present in A/New York/1/1918 and A/London/1/1919, demonstrating the same change I 1918 that has been described in 2009. Although WHO stated that this change was "not significant" in the Ukraine samples, it was associated with the fatal cases and is cause for concern. The concern was increased by the announcement from Norway indicating the same change was found in fatal H1N1 lung infections there also." 1918 RBD D225G in Lung Cases in Ukraine and Norway Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. ----- Oppdatering 22/11/09 kl. 15.00: Som første norske avis skriver Dagbladet i dag at viruset påvist i Norge er identisk med det som er observert i Ukraina. "Fredag advarte norske myndigheter om at en farligere og mutert variant av svineinfluensaviruset var funnet i Norge. Den samme mutasjonen er, ifølge Verdens helseorganisasjon (WHO) registrert i Ukraina. Det har fått norske myndigheter til å reagere. - Vi ble kjent med dette på ryktebørsen, og undersøker om denne mutasjonen er skyld i de mange dødsfallene i Ukraina. Det er tidkrevende arbeid, og vi vet ennå ikke om det er tilfellet, sier overlege Karin Rønning ved avdeling for infeksjonsovervåkning på Folkehelseinstituttet til Dagbladet." Ukraina på dødstoppen - Norge har samme muterte virus Oppdatering 24/11/09 kl. 18.00: Bloggeren Henry Niman skriver i kveld at 25 hemagglutinin-sekvenser fra Norge nå er offentliggjort på GenBank. Seks av disse har RBD (receptor binding domain) endringer. Alle er på posisjon 225. Bare en av sekvensene har D225G som nylig ble påvist i fire sekvenser fra Ukraina. Fem av sekvensene fra Norge har en mindre kjent variant D225E. "Twenty-five HA sequences from Norway have been released at Genbank. The isolates were collected between May and October and include six sequences with receptor binding domain changes. All changes are at position 225, but 5 of the 6 have D225E, which the sixth has D225G as well as wild type D225. Outcomes are not included in the characterization sheet, but it is likely that the two fatal and one serious cases described in media releases last week were samples with D225E." Niman poengterer at D225G kan tenkes å være underrepresentert ved prøvetaking fordi D225G går dypt i lungene, mens prøver ofte tas i øvre luftveier. "The finding of D225G in Norway (A/Norway/2924/2009) as a mixture with wild type sequences confirms that isolates with receptor binding domain changes can be circulating as mixtures and the sequence identified will be dependent on the tissue sampled and when it is sampled. Thus, Infections with a high frequency of D225G will likely be quickly cleared from the upper respiratory tract because viruses with D225G will quickly go to the lungs, which wild type sequences will be more quickly cleared from the upper respiratory tract. Thus a nasopharyngeal swab may be negative if all not cleared virus has moved to the lungs, or be positive for the wild type if depleted wild type H1N1 is remaining at the time of swabbing. Thus, the true level of D225G may be grossly under estimated by nasopharyngeal swabs, and the one sample positive for D225G may reflect the rare instances where D225G could still be detected in a nasopharyngeal swab." H1N1 RBD Changes D225G and D225E in Norway Bakgrunnsartikkel i Wikipedia om Hemagglutinin (forkortes HA). God diskusjon av SusanC på Flu Wiki om endringer som er observert i pandemisk H1N1 2009: "There's been much interest recently in the revelation of 'mutations' in the HA of the 2009 H1N1 virus, specifically, a 'change' at position 225 from D to G (see codon table for coding). I put the words mutation and change in quotes for reasons that will become obvious as you read further. I thought I might as well take this opportunity to review the issue of mutations that favor different patterns of receptor binding, from 1918 to now. " Receptor Binding and Evolutionary Trends of H1N1 HAs Ifølge Aftenposten sendte Folkehelseinstituttet prøver fra 70 pasienter til WHO. Tilsammen 32 sekvenser fra Norge ble publisert i går på GenBank. Alle tilgjengelige sekvenser er med andre ord trolig ikke offentliggjort. Oppdatering 25/11/09 kl. 23.00: "However, 25 HA sequences deposited at Genbank had an HA sequence that contained D225G, A/Norway/2924/2009, but also had the wild type sequence, raising concerns that D225G was circulating as a mixture that was most easily detected in lung samples, because the D225G was more than a "marker". It is a polymorphisms that was found in 1918 and 1919 samples which were well characterized for receptor binding properties, which indicated the change conferred increased binding to gal 2,3 receptors which are present in lung. Concerns that this receptor binding domain change was widely circulating were increased because an HA marker on the Norway isolate with D225G was found on additional isolates in Norway, and worldwide (see list here). This marker was also in the HA sequences from the fatal cases in Ukraine. Full sequences from one of the Norway isolates, A/Norway/3364-2/2009, were deposited, and a marker on the NA sequence matched isolates with the HA marker, linking this broader set of isolate from Norway with the Ukraine sequences, which also had the NA marker, as did multiple other isolates (see list here). These associations link Ukraine to Norway, but the D225G polymorphism has jumped onto multiple genetic backgrounds, which are widespread, increasing concerns the D225G is circulating undetected because it is concentrated in lung tissues and is poorly represented in nasopharyngeal swabs. Release of full sequences from China, as well as Norway, would be useful." D225G Ukraine Norway Link and China Spread Oppdatering 25/11/09 kl. 15.00: Ved å sammenligne informasjon (kjønn/alder/fylke/dato) fra GenBank med offisiell oversikt over dødsfall i Norge er det klart at bare en av sekvensene som Folkehelseinstituttet har publisert kommer fra en omkommet pasient (sekvensen fra 8. september uten oppgitt alder, men som trolig stammer fra en 42 år gammel kvinne fra Akershus som døde 5. september). Denne sekvensen har hverken D225G eller D225E. Dette betyr at Folkehelseinstituttet holder tilbake sekvensene fra de to omkomne som ifølge Folkehelseinstituttet skal ha hatt en mutasjon som gjør at viruset går dypere i lungene. I og med at bare en av sekvensene som er offentliggjort kommer fra en omkommet pasient, ser det ut til at Folkehelseinstituttet, bortsett fra i ett tilfelle, har unnlatt å publisere sekvenser som stammer fra døde pasienter.