On 20 November 2009, the Norwegian Institute of Health has informed the 'WHO the finding of a mutation of the virus H1N1swl in three cases of severe pneumonia. This is the replacement of an amino acid nell'emoagglutinina (H1), which has glycine at position 225 instead of aspartic acid.
In reality, this mutation had been reported since the beginning of the pandemic in Brazil, China, Japan, Mexico, Ukraine and the USA in both clinical forms of mild to severe.
The cases so far reported are sporadic, not linked epidemiologically to one another. Following that report, the National Institute of Health, the revalued sequenze di 100 virus identificati in Italia , l'ha riscontrata in un solo paziente, affetto da una grave forma di polmonite risoltasi dopo ricovero in terapia intensiva e trattamento con ECMO.
Il reale impatto e significato clinico di questa mutazione è difficile da comprendere, attualmente si può ipotizzare, sulla base di precedenti studi sui virus influenzali, che l'emoagglutinina (H1) virale mutata abbia una maggiore capacità di attacco sui recettori delle basse vie respiratorie, recettori selettivamente attaccati dai virus aviari.
Da studi effettuati su virus influenzali stagionali, pandemici e aviari isolati dal 1918 ad oggi emerge anche l'ipotesi che tale mutazione riduca la trasmissione inter-umana con le gocce tract, it seems not to cause a selective advantage for the virus.
There were no changes in the amino acid sequence of the hemagglutinin antigenic determinants, so that this mutation does not change the affinity for the virus of anti-H stimulated by the vaccine.
The mutated virus remains sensitive to zanamivir and oseltamivir, antivirals that act by inhibiting the action of neuraminidase (N1) protein under the control of another gene of the virus.
The ability to bind to cellular receptors, however, characterized the virus H1N1swl, as evidenced by a study published by Childs in September 2009 in Nature Biotehnology. ll professor Shefa Zaki, pathologist of the CDC, analyzed more than 100 samples of autopsy subjects who died inflluenza Pandemic confirmed and found the virus in the cells to a greater extent even than the findings from the cases studied died of H5N1 virus infection. Zaki analyzed to compare the paintings of bird flu infections in immunocompromised to cortisone treatment.
One word about the expected changes of the virus
monitoring genetic sequences of virus isolates is justified by the high probability of mutations that is expected of the influenza virus, more than 1% of the genome of the influenza virus changes every year. Some mutations
expectations related to an increase in pathogenicity of the virus have not yet been identified, such as the release of the stop codon of the PB1-F2 gene , the killer protein, while the E627K mutation of the PB2 , which allows for optimal replication of the virus at 33 ° C (temperature human nose in winter) has already been reported in some cases.
The mutation of the gene for neuraminidase (N1), resulting in substitution of tyrosine in position 274 with histidine is responsible for the acquisition of resistance to oseltamivir (Tamiflu), which has already been reported sporadically. Resistant viruses were isolated mainly in prophylaxis in individuals at risk, it is assumed that the antiviral maintained low dose in the course of infection was not conducive to the block in viral load that any virus with the mutation may continue to replicate and infect the body.
Another exception concerns the replenishment (shift) of the virus with a virus with the seasonal or avian virus H5N1, is a possible event even more rare than the mutation. Reassortment with the emergence of a pandemic virus, which maintains that high diffusibility human to human, is even less likely, is an event that historically has occurred only three times in the last century. Professor Bruno Lina
, a French virologist, was able to get a reassortment between the two viruses H1N1, lo stagionale e il pandemico, inoculandoli in coltura di cellule e sta studiando la patogenicità e trasmissibilità nei topi di questo virus. Non è riuscito invece ad ottenere un riassortimento del virus pandemico con il virus H5N1, esperimento che aveva già provato senza successo con i virus stagionali.
Aggiungo per chi ha curiosità di sapere qualcosa ancora sulla mutazione segnalata
Gli aminoacidi in posizione 225 e 190 sono i principali determinanti dell'affinità del legame tra proteina virale H e recettore della membrana cellulare da infettare; differenti in virus influenzali di diverse specie.
L'acido sialico costituisce the end of the cellular receptor to which it attacks the influenza virus. in human cell membranes, there are two types of sialic acid depending on whether this is linked to carbon in position 2 or 6 of galactose. The bond alpha (2.6) predominates in cells of the upper respiratory tract while the alpha (2.3) predominates in non-ciliated bronchiolar cells and alveolar type II cells. The sialic acid alpha (2.3) in birds predominate in the intestinal cells. Pig tracheal epithelial cells have both receptors, which is why it is assumed that the genetic reassortment between different species may be more likely in these animals, but also the two coexist in the lungs of man receptors.
H The avian virus has selective affinity for the receptor sialic acid-linked alpha (2.3). The H human virus has selective affinity for the one with the sialic acid-linked alpha (2.6)
This seems to depend on different affinity dall'aminoacido in this position 225 of the H protein, is present in avian viruses glycine ( G), prevail in the human viruses aspartic acid (D). The current pandemic influenza virus has Asp225 (marked as D225), except for a few sporadic isolates reported during three severe cases in Norway.
Studies in 2006 on the 1918 influenza virus extracted from biopsy specimens, have shown that the virus A / South Carolina/1918, which has aspartic acid at position 225 (Asp225), only has an affinity for the receptors alpha (2.6), while the virus that has A/NewYork/1918 glycine (Gly225) has affinity for both receptors. The classical strains of avian origin have glycine in position 225 (Gly225) H. exclusively but have selective affinity for the receptor alpha (2.3), the non-affinity receptor alpha (2.6) seems determined by the presence of glutamine in position 190 (Glu190) instead of Asp190 present in the human viruses.
The ability to bind to receptors alpha (2.6) is an indispensable factor for a good transmissibility of the virus by air, with respiratory droplets. The avian virus, then with Glu190 and Gly225 in H, with only selective receptor alpha (2.3) are not able to be transmitted by respiratory droplets. The NY1918 human virus that had affinity for both receptor alpha (2.6) than for alpha (2.3) has a transmission capacity inefficiently. The SC1918
human virus that had affinity only for the receptor alpha (2.6) has an effective transmission capacity.
The H with increased affinity for alpha (2.3) would increase the aggressiveness of the virus but also lead to a reduction in transmission capacity. It seems, therefore, a mutation that no advantage selettivi del virus. Maria Grazia Lunetta
Bibliografia:
- Childs RA et al. Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray. Nature Biotechnology 2009;27:797
- Brendan Maher B et al. Swine flu: One killer virus, three key questions. Nature 462, 154-157 (2009)
- Vincent Racaniello. The D225G change in 2009 H1N1 influenza virus is not a concern. Virology Blog:24 November 2009
- Vincent Racaniello. Influenza virus attachment to cells: role of different sialic acids. Virology Blog: 5 May 2009
- Stevens J et al. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities . J Mol Biol. 2006 Feb 3;355(5):1143-55 http://www.ncbi.nlm.nih.gov/pubmed/16343533
- Revere. Trying to understand the Norwegian swine flu mutations . Effect Measure: November 21, 2009
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