Surveillance of autopsy cases for D222G substitutions in haemagglutinin of the pandemic (H1N1) 2009 virus in Alberta, Canada

Abstract

Pandemic (H1N1) 2009 virus-positive specimens were collected from autopsy patients and matched to pandemic (H1N1) 2009 virus-positive nasopharyngeal specimens from community control patients and pandemic (H1N1) 2009 virus-positive specimens from intensive-care unit (ICU) patients. Specimens were analysed for polymorphisms at amino acid 222 of the haemagglutinin (HA) glycoprotein. Whereas some specimens from autopsy patients were positive for D222N, none was positive for D222G. All control patient specimens were wild-type D222. D222G polymorphisms were also identified in a subset of ICU patients with admixtures of D222G and D222 and of D222N, D222G and D222 present. The relevance of D222N and D222G to influenza pathogenesis and transmissibility currently remains unclear.

Emergent 2009 influenza A(H1N1) viruses containing HA D222N mutation associated with severe clinical outcomes in the Americas

“…Thus, the true prevalence of the D222N variant may be much higher than the handful of D222N sequences in the databases suggest. 16,18 Besides the severe respiratory disease that the three of these patients experienced, all were also lymphopaenic during initial presentation. Lymphopaenia is not an uncommon finding in influenza infection, and it has been noted to be present in infection with both seasonal and pandemic viruses.…”

Evidence of the circulation of pandemic influenza (H1N1) 2009 with D222D/G/N/S hemagglutinin polymorphisms during the first wave of the 2009 influenza pandemic

“…A similar phenomenon was also observed in a subset of ICU patients in Canada. 9 Whether competition among viral quasispecies has any impact on the severity of infection remains unclear. However, in most ICU admissions, pre-existing medical conditions appear to be the main contribution to severity rather than particular viral variants.…”

In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient

“…Early during the 2009 pandemic, amino acid polymorphisms in the receptor binding domain of the hemagglutinin gene (HA) were identified(Chutinimitkul et al, 2010; Kilander et al, 2010; WHO, 2010), and an association was made with severe disease or fatal outcomes (Kilander et al, 2010). Specifically, reports have documented an association with severe influenza and isolation of pandemic viruses with position 222 mutations from the consensus Aspartic acid (D) to either Glycine (G) or Asparagine (N) (Baldanti et al, 2010; Baumeister et al, 2010; Drews et al, 2010; Ertek et al, 2010; Ikonen et al, 2010; L’Vov D et al, 2010; Potdar et al, 2010; Puzelli et al, 2010; Wang et al, 2011). Another variant codon at position 222, Glutamic acid (E), has been observed but has not been associated with severe disease (Puzelli et al, 2010).…”