ABSTRACT
The association between a particular mutation in the HA1 subunit of the influenza virus haemagglutinin, D222G, and severe and fatal disease in cases of influenza A(H1N1)pdm09 in Norway during the 2009 pandemic was investigated using pyrosequencing. The prevalence of the variant among fatal cases was 8/26 and among severe non-fatal cases 5/52. No D222G mutations were found among the 381 mild cases. This difference could not be attributed to sampling differences, such as body location of sampling, or duration of illness. In cases with mutant virus where clinical specimens from different days of illness were available, transition from wild-type to mutant virus was commonly observed (4/5), indicating that the mutant virus emerged sporadically in individual patients. In patients with paired samples from both the upper and lower respiratory tract (n=8), the same viral genotypes were detected in both locations. In most of the D222G cases (11/13), the mutant virus was found as a quasispecies.
Subject(s)
Genetic Variation/genetics , Hemagglutinins, Viral/genetics , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/virology , RNA, Viral/genetics , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Genotype , Humans , Infant , Infant, Newborn , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human/epidemiology , Male , Middle Aged , Molecular Sequence Data , Norway/epidemiology , Pandemics , Population Surveillance , Prevalence , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Sex Distribution , Young AdultABSTRACT
Infection with the recently emerged pandemic influenza A(H1N1) virus causes mild disease in the vast majority of cases, but sporadically also very severe disease. A specific mutation in the viral haemagglutinin (D222G) was found with considerable frequency in fatal and severe cases in Norway, but was virtually absent among clinically mild cases. This difference was statistically significant and our data are consistent with a possible causal relationship between this mutation and the clinical outcome.
