Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010

Kilander, Anette; Rykkvin, Rikard; Dudman, Susanne; Hungnes, Olav

doi:10.2807/ese.15.09.19498-en

Cited by 198 publications

(232 citation statements)

References 4 publications

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“…The CT-Sw/1204 virus also became virulent in BALB/c mice known to express predominantly α2,3-sialic acid in their lungs (24), and demonstrated enhanced infectivity and growth in human lung tissues, indicating potentially productive pulmonary replication. Notably, severe viral pneumonia attributed to efficient virus attachment to α2,3-sialic acid glycoconjugates deep in the lungs have been observed in H5N1 (25) and HA 225G variants of the pH1N1 (5,(26)(27)(28)(29)(30) virus infections. Moreover, it has been demonstrated that avian-type receptor-binding ability because of HA 225G increased pathogenicity of the pH1N1 2009 virus in nonhuman primates (31).…”

Section: Discussionmentioning

confidence: 99%

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Pascua

Song

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA 225G and NA 315N substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA 225G and NA 315N as potential virulence markers in mammals.

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Section: Discussionmentioning

confidence: 99%

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Pascua

Song

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…This lack of drift was reflected in the World Health Organization's (WHO) Vaccine formulation decisions which recommended an A/California/7/2009-like pandemic influenza A(H1N1) virus for both the southern hemisphere 2010 and the northern hemisphere 2010-11 influenza vaccines [2]. While some genetic variants have been reported such as the D222G (D239G numbering if starting at the first methionine) HA mutation which was linked with more severe outcomes following pandemic influenza virus infection [3] and a more commonly seen E391K change in the HA gene [4] during late 2009, no clear variant has predominated in a country or region and no vaccine update has been forthcoming. This report, however, describes the recent emergence in Singapore and subsequent spread of a genetic variant of the pandemic influenza A(H1N1) virus to Australia and New Zealand during their 2010 winter influenza season, where it now predominates and has been detected in some vaccine breakthroughs and fatal cases.…”

Section: Research Articlesmentioning

confidence: 99%

A new pandemic influenza A(H1N1) genetic variant predominated in the winter 2010 influenza season in Australia, New Zealand and Singapore

et al. 2010

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Pandemic H1N1 influenza virus is of global health concern and is currently the predominant influenza virus subtype circulating in the southern hemisphere 2010 winter. The virus has changed little since it emerged in 2009, however, in this report we describe several genetically distinct changes in the pandemic H1N1 influenza virus. These variants were first detected in Singapore in early 2010 and have subsequently spread through Australia and New Zealand. At this stage, these signature changes in the haemagglutinin and neuraminidase proteins have not resulted in significant antigenic changes which might make the current vaccine less effective, but such adaptive mutations should be carefully monitored as the northern hemisphere approaches its winter influenza season.

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“…Instead, R591 is reported to compensate for it and is responsible for infecting humans (Medina and Garcia-Sastre, 2011;Mehle and Doudna, 2009;Yamada et al, 2010). Interestingly, patients infected with the 2009 pandemic virus with D222G mutation in hemagglutinin exhibited severe forms of the disease, such as pneumonia, suggesting that this mutation may have increased viral virulence (Kilander et al, 2010). However, subsequent studies revealed that the 2009 pandemic virus with only this mutation exhibited no significant increase in receptor binding, pathogenesis or transmissibility (Belser et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Multiple amino acid mutations in viral RNA polymerase may synergistically enhance the transmissibility and/or virulence of the 2009 pandemic influenza (H1N1) virus

Wang¹,

Zhou²,

Chen³

et al. 2013

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Summary. -Influenza viruses may change their transmissibility and virulence via single or multiple point mutations in the functional regions of their structural proteins. In this study, we compared sequences of all three subunits of viral RNA polymerase, i.e. PA, PB1 and PB2, of the 2009 pandemic influenza A (H1N1) virus isolates from different stages of the pandemic and found that the frequencies of three mutations, including V14I and K716Q in PA and K736G in PB1, showed a similar trend. Interestingly, the death rate of infected patients during the pandemic matched the frequency of the three mutations with a 2-months delay. These findings suggest that the combined mutations may have acted synergistically in enhancing the transmissibility and/or virulence of the 2009 pandemic virus. If definitely proved, this hypothesis could guide the rational design of antiviral therapeutics targeting the RNA polymerase of influenza viruses.

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Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010

Cited by 198 publications

References 4 publications

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

A new pandemic influenza A(H1N1) genetic variant predominated in the winter 2010 influenza season in Australia, New Zealand and Singapore

Multiple amino acid mutations in viral RNA polymerase may synergistically enhance the transmissibility and/or virulence of the 2009 pandemic influenza (H1N1) virus

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