# 5018
From Eurosurveillance yesterday, another report on mutations in the novel H1N1 virus that may be associated with increased virulence.
The operative word here being `may’.
The main thrust of this report is on the rare, so-called `Norway’ mutation (D222G), but it also looks at a more common mutation; (D222E).
The D222G mutation involves a single amino acid change in the HA1 gene at position 222 from aspartic acid (D) to glycine (G).
The D222E mutation is the switching to glutamic acid (E) from aspartic acid (D) in the same location.
First the link, then some excerpts and discussion. The entire report is worth reading.
Puzelli S, Facchini M, De Marco MA, Palmieri A, Spagnolo D, Boros S, Corcioli F, Trotta D, Bagnarelli P, Azzi A, Cassone A, Rezza G, Pompa MG, Oleari F, Donatelli I, the Influnet Surveillance Group for Pandemic A(H1N1) 2009 Influenza Virus in Italy.
Euro Surveill. 2010;15(43):pii=19696.
A daunting title to be sure, but once you get past that, it gets a bit easier. Here then is the Abstract:
Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance.
Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%).
A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.
Influenza viruses are inherently unstable, and are therefore prone to replication errors.
Amino acids can get substituted somewhere in the virus’s protein, and that can affect virulence, receptor binding, sensitivity to antivirals, and transmission.
Most mutations go nowhere.
They do nothing to enhance the virus, and may actually decrease its ability to replicate, transmit, or compete with other strains.
Quite frankly, mutations happen all the time and are often of little consequence.
Most are evolutionary dead-ends.
But with millions of infected hosts sporting trillions and trillions of (sometimes badly) replicated viruses, this genetic roulette wheel has ample opportunities to test out new and potentially viable amino acid combinations.
Mutations can happen spontaneously in an infected host, and only affect that individual. Or . . . if the mutated virus is `biological fit’ and easily transmitted – it may move onto other hosts as well.
Complicating matters - viruses can have multiple amino acid changes – and the combination of these changes can unpredictably (at least for now) alter the virus’s behavior.
Thus far, the D222G mutation has only shown up rarely (less than 2% of samples), and serious questions over its ability to transmit easily from human-to-human remain.
Recent studies have suggested that it may be linked to more severe pulmonary infections (see D222G And Deep Lung Infections), and that it may have a binding affinity for α2-3 receptor cells found in the lower respiratory system.
In this most recent study of 169 patients from Italy, the D222G substitution was found in 3 of 52 (5.8%) of severe cases and in only 1 of 117 (0.9%) of mild cases.
While suspiciously more common in severely ill patients, the authors state that these results (and the limited dataset) are too small to conclude that they are statistically significant.
It should be noted that the one mild case with this mutation also had a concurrent G155E mutation. Whether this was a contributing factor to D222G appearing in a mildly ill patient is unknown.
The D222E mutation was far more common, and fairly evenly divided between severe cases (38.5%) and mild cases (31.6%). All of which means that the clinical impact (if any) of this mutation remains unknown.
This increased prevalence, along with the detection of a cluster of D222E mutations in a group of mildly ill high school students (described in this paper) suggests some degree of inter-human transmission.
The authors wrap up their report with this:
Finally, our data suggest that the D222G substitution is overall rather infrequent, even among severe cases. However, we confirm that it occurs with a higher frequency in severe cases.
Whether this association is indicative of higher virulence or is the consequence of receptor-specific adaptive mutation needs to be further investigated.
All of which means that while we continue to get more and very useful data - we don’t have a lot of answers yet.
Stay tuned.
For more on pdmH1N1 mutations, you may wish to revisit:
Eurosurveillance On Recently Isolated H1N1 Mutations
Study: Receptor Binding Changes With H1N1 D222G Mutation
WER Review: D222G Mutation In H1N1
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