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Euro Surveill. Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 20

Giuseppe

Emeritus
Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10 (Euro Surveill., letter, extract, edited)

[Source: EuroSurveillance, full text (LINK). Extract, edited.]

Eurosurveillance, Volume 15, Issue 16, 22 April 2010

Letters

Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10

R S Miller 1, A R MacLean 1, R N Gunson 1, W F Carman 1
1. West of Scotland Specialist Virology Centre, Glasgow, United Kingdom

Citation style for this article: Miller RS, MacLean AR, Gunson RN, Carman WF. Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10. Euro Surveill. 2010;15(16):pii=19546. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19546

Date of submission: 19 April 2010


To the editor:

Kilander et al. (2010) [1] have previously reported that in some cases of patients with severe or fatal pandemic influenza A(H1N1), an amino acid substitution from aspartic acid to glycine occurs at position 222 (D222G) of the HA1 subunit of haemagglutinin (HA). In their study 11 (18%) of 61 patients with severe disease had the mutation, in contrast to 0 of 205 patients with mild disease.

Since the original report [1] several countries have detected this mutation [2]. This data has been summarised in a recent World Health Organization (WHO) review, which reported that the overall prevalence of D222G was <1.8% in contrast to a rate of 7.1% in fatal cases [2]. The WHO paper also reports on the occurrence of other mutations at this amino acid, D222E and D222N, although their significance is unclear. A group in Hong Kong have also analysed this amino acid in severe and non-severe cases of pandemic influenza A(H1N1) [3]. In this study nine (4.1%) of 219 severe or fatal cases of pandemic influenza A(H1N1) had the D222G mutation, in contrast to 0 of 239 non-severe cases.

We sequenced the HA1 subunit of the HA gene from a number of West of Scotland cases, both community cases and severely ill. Furthermore we subdivided the severely ill into those who had died and those who recovered after hospitalisation. We found an increased incidence of D222G in those patients who died (2/23 - 8.7%) compared to both community and hospitalised patients (0/35 - 0%). We also detected an increased incidence (2/32 - 6.2% cf 0/26 - 0%) of D222N (aspartic acid to asparigine) in severely ill patients and those who had died. The significance of this mutation is unclear. There was a low level of D222E (aspartic acid to glutamic acid) present in both severely ill and community cases with no significant difference between the two. The results are summarised in the Table.

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Re: Euro Surveill. Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10 (letter)

Interestingly, in one of the patients who died and had the D222G mutation, the original sequence had a mixed base in the D222 codon giving D222D/G. On resequencing two more samples from this patient, we obtained a pure D222G on one occasion and a pure wildtype D222 on the other, showing that this patient had a mixed population of virus. This confirms the finding in Kilander’s paper [1] of the co-existence of mutant and wildtype virus.

3 passages, 3 different results?
 
Re: Euro Surveill. Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10 (letter)

is 225G present early in the disease ? or only in lung autopsies
 
Re: Euro Surveill. Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009-10 (letter)

is 225G present early in the disease ? or only in lung autopsies

Remember this pig study: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009068#pone.0009068-Reid1

They innoculated pigs with a strain containing 225X and 226X (grt and cra). In the pigs, it went to grt, caa and after transmission had gat & caa (D225 & Q226). But when they took lung samples, at 1 & 2 dpi it was still grt & caa but on days 4 & 7 it was ggt (D225G) & caa (Q226).

Comments from the study:
Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G).

So why was D225 detected in the nasal secretions of contact pigs but the directly innoculated ones had 225G by day 4?
 
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