Discussion: Mutation D222N was also associated with severe disease and fatality, but this association was not statistically significant and the study did not show any association of D222E with severe disease.
Discussion: While D222G/N mutations are often associated with severe disease and mortality, the association of D222Y/A/V/E mutations with the severity of the disease has not been established.
In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.
Result: Known polymorphisms, namely S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in all but one (pt2) patients; five further non polymorphic variants were detected at frequency >40%, namely three within HA,
Result: This analysis showed that seven HA minority variants (Q188R/N194S/N194D/D222E/Q223R/E224G/T245N) may play a role in the host specificity shift and that two (S190G/Q223R) are related to antigenic drift and/or escape mutant.
Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.
PMID: 25966032
2015
Influenza and other respiratory viruses
Introduction: For example, the amino acid substitution at position D222G/E/N (H1 numbering) in the HA molecule was associated with increased viremia, severe pneumonia, and deaths; a substitution (I219K) in the glycan receptor-binding site of HA quantitatively increased its human receptor-binding affinity; and substitutions D131E, S186, and A198E contribute to virulence in mice.
Discussion: Similar to the D222G mutation, the variants D222A, D222E, and D222N also result in enhanced binding to receptor (alpha2-3) of epithelial cells in the lower respiratory tract, whereas wild-type seasonal
Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants.
Discussion: The HA D222G/E/N substitution increases the intensity of binding for SAalpha-2,6 and alters the HA-NA balance which may decrease viral fitness in a SAalpha-2,6 environment.
Discussion: This is the first report, to our knowledge, that has studied the functional balance of HA-NA in human strains regarding the impact of the D222G/N/E substitution on SAalpha-2,6 HA binding.
Discussion: This may explain why D222G and also D222E/N viruses are not able to be transmitted efficiently and are isolated only sporadically.
Detection of haemagglutinin D222 polymorphisms in influenza A(H1N1)pdm09-infected patients by ultra-deep pyrosequencing.
PMID: 22862843
2013
Clinical microbiology and infection
Abstract: D222G/N/A were detected, as either minor or predominant variants, only in severe cases, whereas D222E was equally represented in severe and moderate-mild infections.
Abstract: D222E, D222G, D222N and D222A were observed in 37.0%, 11.1%, 7.4% and 3.7% of patients, respectively; 10.7% of samples harboured more than two variants.
Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen, China.
Introduction: In contrast, for many mutations that have arisen, including S143G, S185T, A134T, D222E, P297S and E374K, there exists little data reported other than epidemiology, phylogeny, and some limited antigenicity studies.
Result: Variant 3 is a double mutant (D222E and P297S) that appeared in late 2009, reaching its maximum in 2010 but declined afterwar
Table: D222E
Figure: Effect of D222E in receptor binding.
Figure: In D222E, only K219 and E224 interact with galactose, while E222 interacts through water-mediated hydrogen bonds with nearby glycosylations originating at N87.
Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011.
Abstract: D222E substitution was found in virus taken from one patient with severe clinical syndrome (2%) out of 42 severe cases analyzed and E374K substitution was found in two severe cases (4%) out of 42 severe cases studied.
Result: Moreover, D222E was found in one out of 50 viruses studied.
Table: D222E
Discussion: Despite the available virological, epidemiological and clinical information, the D222E substitution could confer more severity to the disease.
Discussion: The D222E was detected with less frequency than the D222G and only found in severe case patient.
Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010.
IV mutation literature information.
PMID: 
2021
PloS one
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