Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Short report

Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011

Authors: Awatef El Moussi, Mohamed Ali Ben Hadj Kacem, Francisco Pozo, Juan Ledesma, Maria Teresa Cuevas, Inmaculada Casas, Amine Slim

Published in: Diagnostic Pathology | Issue 1/2013

Login to get access

Abstract

Background

The novel pandemic A (H1N1) pdm09 virus was first identified in Mexico in April 2009 and since then it spread worldwide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the haemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pathogenicity.

Methods

To monitor the genetic polymorphisms at position 222 of Haemagglutinin of influenza A(H1N1)pdm09 viruses from both outpatients with mild influenza and individuals with severe disease requiring hospitalization, during 2009–2010 and 2010–2011 seasons, a sequence-based genotypic assessment of viral populations to understand the prevalence of D222G mutation.

Results

The D222G was identified in clinical specimens from 3 out of 42 cases analyzed in Tunisia with severe outcome (7%). Interestingly, in one fatal case out of four viruses taken from fatal cases studied (25%). Also this mutation was found in one mild case out of 8 mild cases studied (0.1%). 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.

Conclusions

A specific mutation in the viral haemagglutinin (D222G) was found in fatal, severe and mild case. Further virological, clinical and epidemiological investigations are needed to ascertain the role of this and other mutations that may alter the virulence and transmissibility of the pandemic influenza A (H1N1)pdm09.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1027334947811255​
Appendix
Available only for authorised users
Literature
1.
Miller MA, Viboud C, Balinska M, Simonsen L: The signature features of influenza pandemics–implications for policy. N Engl J Med. 2009, 360 (25): 2595-2598. 10.1056/NEJMp0903906.CrossRefPubMed
2.
Neumann G, Noda T, Kawaoka Y: Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature. 2009, 459 (7249): 931-939. 10.1038/nature08157.PubMedCentralCrossRefPubMed
3.
Ikonen N, Haanpaa M, Ronkko E, Lyytikainen O, Kuusi M, Ruutu P, Kallio-Kokko H, Mannonen L, Lappalainen M, Ziegler T, Julkunen I: Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland. PLoS One. 2010, 5 (10): e13329-10.1371/journal.pone.0013329.PubMedCentralCrossRefPubMed
4.
Kuroda M, Katano H, Nakajima N, Tobiume M, Ainai A, Sekizuka T, Hasegawa H, Tashiro M, Sasaki Y, Arakawa Y, Hata S, Watanabe M, Sata T: Characterization of quasispecies of pandemic 2009 influenza A virus (A/H1N1/2009) by de novo sequencing using a next-generation DNA sequencer. PLoS One. 2010, 5 (4): e10256-10.1371/journal.pone.0010256.PubMedCentralCrossRefPubMed
5.
Puzelli S, Facchini M, Spagnolo D, De Marco MA, Calzoletti L, Zanetti A, Fumagalli R, Tanzi ML, Cassone A, Rezza G, Donatelli I: Surveillance Group for Pandemic A H1N1 2009 Influenza Virus in Italy: Transmission of hemagglutinin D222G mutant strain of pandemic (H1N1) 2009 virus. Emerg Infect Dis. 2010, 16 (5): 863-865. 10.3201/eid1605.091858.PubMedCentralCrossRefPubMed
6.
Chutinimitkul S, Herfst S, Steel J, Lowen AC, Ye J, van Riel D, Schrauwen EJ, Bestebroer TM, Koel B, Burke DF, Sutherland-Cash KH, Whittleston CS, Russell CA, Wales DJ, Smith DJ, Jonges M, Meijer A, Koopmans M, Rimmelzwaan GF, Kuiken T, Osterhaus AD, García-Sastre A, Perez DR, Fouchier RA: Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol. 2010, 84 (22): 11802-11813. 10.1128/JVI.01136-10.PubMedCentralCrossRefPubMed
7.
Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, Daniels R, Gregory V, Uhlendorff J, Kiso M, Klenk HD, Hay A, Feizi T, Matrosovich M: Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus. J Virol. 2010, 84 (22): 12069-12074. 10.1128/JVI.01639-10.PubMedCentralCrossRefPubMed
8.
Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y: Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol. 2000, 74 (18): 8502-8512. 10.1128/JVI.74.18.8502-8512.2000.PubMedCentralCrossRefPubMed
9.
Tumpey TM, Maines TR, Van Hoeven N, Glaser L, Solorzano A, Pappas C, Cox NJ, Swayne DE, Palese P, Katz JM, García-Sastre A: A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science. 2007, 315 (5812): 655-659. 10.1126/science.1136212.CrossRefPubMed
10.
Kao CL, Chan TC, Tsai CH, Chu KY, Chuang SF, Lee CC, Li ZR, Wu KW, Chang LY, Shen YH, Huang LM, Lee PI, Yang C, Compans R, Rouse BT, King CC: Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009–10. PLoS One. 2012, 7 (2): e31162-10.1371/journal.pone.0031162.PubMedCentralCrossRefPubMed
11.
Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA: Antibody recognition of a highly conserved influenza virus epitope. Science. 2009, 324 (5924): 246-51. 10.1126/science.1171491.PubMedCentralCrossRefPubMed
12.
Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA: Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009, 16 (3): 265-273. 10.1038/nsmb.1566.PubMedCentralCrossRefPubMed
13.
14.
Ledesma J, Pozo F, Ruiz MP, Navarro JM, Piñeiro L, Montes M, Castro SP, Fernández JS, Costa JG, Fernández M, Galán JC, Cuevas MT, Casas I, Breña PP: Spanish Influenza Surveillance System (SISS): Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1)2009 viruses in Spain. J Clin Virol. 2011, 51 (1): 75-8. 10.1016/j.jcv.2011.01.020.CrossRefPubMed
15.
Tamura K, Dudley J, Nei M, Kumar S, MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 2007, 24 (8): 1596-1599. 10.1093/molbev/msm092.CrossRefPubMed
16.
Kilander A, Rykkvin R, Dudman SG, Hungnes O: Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009–2010. Euro Surveill. 2010, 15 (9): 19498-PubMed
17.
Miller RR, MacLean AR, Gunson RN, Carman WF: Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1) infected patients in the West of Scotland, United Kingdom, 2009–10. Euro Surveill. 2010, 15 (16): 19546-PubMed
18.
Zhang Y, Sun H, Fan L, Ma Y, Sun Y, Pu J, Yang J, Qiao J, Ma G, Liu J:Acute respiratory distress syndrome Induced by a swine 2009 H1N1 variant in mice. PLoS One. 2012, 7 (1): e29347-10.1371/journal.pone.0029347.PubMedCentralCrossRefPubMed
19.
El Moussi A, Ledesma J, Ben Hadj Kacem MA, Pozo F, Cuevas MT, Hamdoun M, Casas I, Perez-Breña P, Slim A: Haemagglutinin D222G mutation found in a fatal case of pandemic (H1N1) flu in Tunisia. Arch Virol. 2012, 157 (9): 1813-4. 10.1007/s00705-012-1349-0.CrossRefPubMed
20.
Malato L, Llavador V, Marmier E, Youssef J, Balick Weber C, Rozé H, Bessede E, Fleury HJ: Pandemic influenza A(H1N1)2009: molecular characterisation and duration of viral shedding in intensive care patients in Bordeaux, south-west France, May 2009 to January 2010. Euro Surveill. 2011, 16 (4): 19776-PubMed
21.
Chan PK, Lee N, Joynt GM, Choi KW, Cheung JL, Yeung AC, Lam P, Wong R, Leung BW, So HY, Lam WY, Hui DC: Clinical and virological course of infection with haemagglutinin D222G mutant strain of 2009 pandemic influenza A (H1N1) virus. J Clin Virol. 2011, 50 (4): 320-4. 10.1016/j.jcv.2011.01.013.CrossRefPubMed
22.
Melidou A, Gioula G, Exindari M, Chatzidimitriou D, Diza E, Malisiovas N: Molecular and phylogenetic analysis of the haemagglutinin gene of pandemic influenza H1N1 2009 viruses associated with severe and fatal infections. Virus Res. 2010, 151 (2): 192-9. 10.1016/j.virusres.2010.05.005.CrossRefPubMed
23.
World Health Organization: Preliminary review of D222G amino acid substitution in the haemagglutinin of pandemic influenza A(H1N1) 2009 viruses. Wkly Epidemiol Rec. 2010, 85 (4): 21-2.
24.
Baldanti F, Campanini G, Piralla A, Rovida F, Braschi A, Mojoli F, Iotti G, Belliato M, Conaldi PG, Arcadipane A, Pariani E, Zanetti A, Minoli L, Emmi V: Severe outcome of influenza A/H1N1/09v infection associated with 222 G/N polymorphisms in the haemagglutinin: a multicentre study. Clin Microbiol Infect. 2011, 17 (8): 1166-9. 10.1111/j.1469-0691.2010.03403.x.CrossRefPubMed
25.
Xu L, Bao L, Lv Q, Deng W, Ma Y, Li F, Zhan L, Zhu H, Ma C, Qin C: A single-amino-acid substitution in the HA protein changes the replication and pathogenicity of the 2009 pandemic A (H1N1) influenza viruses in vitro and in vivo. Virol J. 2010, 7: 325-10.1186/1743-422X-7-325.PubMedCentralCrossRefPubMed
26.
Chan KH, Zhang AJ, To KK, Chan CC, Poon VK, Guo K, Ng F, Zhang QW, Leung VH, Cheung AN, Lau CC, Woo PC, Tse H, Wu W, Chen H, Zheng BJ, Yuen KY: Wild type and mutant 2009 pandemic influenza A(H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice. PLoS One. 2010, 5 (10): e13757-10.1371/journal.pone.0013757.PubMedCentralCrossRefPubMed
27.
Grant MPY, Puzelli S, Facchini M, Spagnolo D, De Marco MA, Calzoletti L, Zanetti A, Fumagalli R, Tanzi ML, Cassone A, Rezza G, Donatelli I: Surveillance Group for Pandemic A H1N1 2009 Influenza Virus in Italy: Transmission of hemagglutinin D222G mutant strain of pandemic (H1N1) 2009 virus. Emerg Infect Dis. 2010, 16 (5): 863-865. 10.3201/eid1605.091858.CrossRef
Metadata
Title
Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011
Authors
Awatef El Moussi
Mohamed Ali Ben Hadj Kacem
Francisco Pozo
Juan Ledesma
Maria Teresa Cuevas
Inmaculada Casas
Amine Slim
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-124

Other articles of this Issue 1/2013

Diagnostic Pathology 1/2013 Go to the issue

Case Report

Anal phyllodes tumor in a male patient: a unique case presentation and literature review

Research

Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer

Methodology

A new method for measuring the psychoacoustical properties of tinnitus

Research

Triggering receptor expressed on myeloid cells − 1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis

Research

Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer

Short report

Right-sided rhabdoid colorectal tumors might be related to the Serrated Pathway