Frequency of D222G and Q223R Hemagglutinin Mutants of Pandemic (H1N1) 2009 Influenza Virus in Japan between 2009 and 2010

Yasugi, Mayo; Nakamura, Shota; Daidoji, Tomo; Kawashita, Norihito; Ramadhany, Ririn; Yang, Cheng-Song; Yasunaga, Teruo; Iida, Tetsuya; Horii, Toshihiro; Ikuta, Kazuyoshi; Takahashi, Kazuo; Nakaya, Takaaki

doi:10.1371/journal.pone.0030946

Cited by 21 publications

(31 citation statements)

References 25 publications

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“…Our results support the suggestion that substitution at HA position 222 is associated with pdm09 pathogenicity, with variants appearing spontaneously during the two pandemic waves in Mexico. Some reports and sequence data have demonstrated that 222 variants appeared in the early phases of the pandemic, increased during 2009–2010 influenza season and have reduced to their present levels during 2010–2011 and 2011–2012 influenza season [30,31]. Bacterial infection or coexisting conditions do not appear to be major contributing factors to the severity (Table 2).…”

Section: Discussionmentioning

confidence: 99%

A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico

Vázquez-Pérez

Iša²,

Kobasa

et al. 2013

Virol J

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BackgroundPandemic type A (H1N1) influenza arose in early 2009, probably in Mexico and the United States, and reappeared in North America in September for seven more months. An amino acid substitution in the hemagglutinin (HA), D222G, has been reported in a significant proportion of patients with a severe and fatal outcome. We studied the prevalence of HA222 substitutions in patients in Mexico during the second wave and its association with clinical outcome and pathogenicity in a mouse model.MethodsThe nucleotide sequences of hemagglutinin (HA) from viruses collected from 77 patients were determined including 50 severe and fatal cases and 27 ambulatory cases. Deep sequencing was done on 5 samples from severe or fatal cases in order to determine the quasispecies proportion. Weight loss and mortality due to infection with cultured influenza viruses were analyzed in a mouse model.ResultsViruses from 14 out of 50 hospitalized patients (28%) had a non aspartic acid residue at the HA 222 position (nD222), while all 27 ambulatory patients had D222 (p = 0.0014). G222 was detected as sole species or in coexistence with N222 and D222 in 12 patients with severe disease including 8 who died. N222 in coexistence with D222 was detected in 1 patient who died and co-occurrence of A222 and V222, together with D222, was detected in another patient who died. The patients with a nD222 residue had higher mortality (71.4%), compared to the group with only D222 (22.2%, p = 0.0008). Four of the 14 viruses from hospitalized patients were cultured and intranasally infected into mice. Two viruses with G222 were lethal while a third virus, with G222, caused only mild illness in mice similar to the fourth virus that contained D222.ConclusionsWe confirm the elevated incidence of HA222 (H1N1)pdm09 variants in severe disease and mortality. Both clinical and mouse infection data support the idea that nD222 mutations contribute to increased severity of disease but additional determinants in disease outcome may be present.

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Section: Discussionmentioning

confidence: 99%

A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico

Vázquez-Pérez

Iša²,

Kobasa

et al. 2013

Virol J

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“…However, the severity of the disease can be affected by a number of other factors. In humans, several specimens possessing D222G substitution were also obtained from mild H1N1pdm cases during the first (May 2009) and second (Dec 2010) waves of the epidemic in Japan (21). In addition to the D222G substitution, two other changes D187E and Q223R were recognised.…”

Section: Discussionmentioning

confidence: 99%

Substitution in position 222 of haemagglutinin of pandemic influenza A (H1N1) viruses isolated from pigs in Poland

Kowalczyk

Urbaniak

Markowska-Daniel

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

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The aim of the study was to monitor genetic diversity and antigenic changes in the genome of influenza A(H1N1)pdm09 viral isolates detected during the post-pandemic period in Poland. Clinical specimens obtained from three suspected cases of influenza were analysed by sequencing. Among the differences identified in amino acids sequences, nine substitutions were located within the antigenic HA1 sites and in five residues forming receptor-binding pocket. The HA(D222G) mutation was shown in the isolate Swine/Poland/134312/12 obtained from a mild case of the disease. It must be emphasized that, in general, clinically mild cases are caused by the viruses in which that specific mutation, i.e. haemagglutinin (D222G), does not occur.

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“…Newly emergent influenza A viruses may have been dual specific but not exclusively α2,6-SA-specific during the early phase of the pandemic and adapted during multiple cycles of human-to-human transmission (Yasugi et al, 2012). Further investigation is required to determine the proportion of α2,3-tropic and α2,6-tropic viruses found in tissues and organs infected with other human-, avian-, and swine-derived influenza viruses.…”

Section: Discussionmentioning

confidence: 99%

Tropism of Pandemic 2009 H1N1 Influenza a Virus

Ramadhany¹,

Yasugi²,

Nakamura³

et al. 2012

Front. Microbio.

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Substitutions at the receptor-binding site of the pandemic H1N1 2009 influenza A virus (H1N1pdm) hemagglutinin (HA) gene may be critical in determining whether a virus binds to human or avian receptors. Previous reports suggest that HA Gly222 and/or Arg223 allow viruses to bind preferentially to the α2,3-linked sialic acid found in avian species. We also demonstrated that serial passaging of influenza A virus in embryonated chicken eggs increased viral growth 32- to 64-fold, coincident with the increased prevalence of Gly222 or Arg223 in HA protein (Yasugi et al., 2012). In this study, we showed that the minor genotype of α2,3-linkage-tropic viruses in upper airways became dominant after passaging through chicken eggs. Viruses possessing HA containing N125D-Q223R, N125D-D187E-Q223R, K119N-D222G, and K119N-N129S-D222G, were detected in both clinical specimens and egg-passaged samples. These results might suggest that egg-adapted viruses, likely represented by α2,3-linkage-tropic virus, were also present in human upper airways as a minor population and transmitted in humans during the outbreak of H1N1pdm.

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Frequency of D222G and Q223R Hemagglutinin Mutants of Pandemic (H1N1) 2009 Influenza Virus in Japan between 2009 and 2010

Cited by 21 publications

References 25 publications

A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico

A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico

Substitution in position 222 of haemagglutinin of pandemic influenza A (H1N1) viruses isolated from pigs in Poland

Tropism of Pandemic 2009 H1N1 Influenza a Virus

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