Emergent 2009 influenza A(H1N1) viruses containing HA D222N mutation associated with severe clinical outcomes in the Americas.
BACKGROUND
During the 2010-2011 influenza season, a small sub-group of 2009 influenza A(H1N1) viruses (hereafter referred to as 2009 A(H1N1)) emerged that was associated with more severe clinical outcomes in Ecuador and North America. Genetically, the haemagglutinin (HA) of this sub-clade was distinct from HAs found in viruses associated with severe outbreaks in 2010 from the United Kingdom and from other global specimens isolated earlier in the season.


OBJECTIVE
We report the emergence of a novel 2009 A(H1N1) variant possessing a re-emergent HA D222N mutation obtained from patients with severe respiratory illnesses and phylogenetically characterise these D222N mutants with other severe disease-causing variants clustering within a common emerging sub-clade.


METHODS
In early 2011, three cases of 2009 A(H1N1) infection, two from Quito, Ecuador, and one from Washington, DC, USA, were complicated by severe pneumonia requiring mechanical ventilation, resulting in one fatality. These cases were selected due to the reported nature of the acute respiratory distress (ARD) that were captured in Department of Defence (DoD)-sponsored global influenza surveillance nets.


RESULTS
Genetically, the 2009 A(H1N1) strains isolated from two of the three severe cases carried a prominent amino acid change at position 222 (D222N) within the primary HA receptor binding site. Furthermore, these cases represent an emerging sub-clade of viruses defined by amino acid changes within HA: N31D, S162N, A186T and V272I. Phylogenetically, these viruses share a high degree of homology with strains associated with recent fatal cases in Chihuahua, Mexico.


CONCLUSIONS
Previously, enhanced virulence associated with the change, D222G, has been clinically linked to severe morbidity and mortality. Initial observations of the prevalence of a novel sub-clade of strains in the Americas suggest that viruses with a re-emergent D222N mutation may too correlate with severe clinical manifestations. These findings warrant heightened vigilance for emerging sub-clades of 2009 A(H1N1) and presumptive clinical implications.
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. huo-shu.houng@amedd.army.mil
Huo-Shu H
HS
Houng
Jason
J
Garner
Yanfei
Y
Zhou
Arthur
A
Lyons
Robert
R
Kuschner
Gregory
G
Deye
Kristina
K
St Clair
Richard W
RW
Douce
Wilson
W
Chicaiza
Patrick J
PJ
Blair
Christopher A
CA
Myers
Ronald L
RL
Burke
Jose L
JL
Sanchez
Maya
M
Williams
Eric S
ES
Halsey
D000328:Adult; D019943:Amino Acid Substitution; D001665:Binding Sites; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000821:virology; D004219:District of Columbia / Q000453:epidemiology; D004484:Ecuador / Q000453:epidemiology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D011014:Pneumonia / Q000453:epidemiology / Q000821:virology; D011991:Receptors, Virus / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000821:virology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus