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01-10-2019 | Original Investigation

Identification of complement-related host genetic risk factors associated with influenza A(H1N1)pdm09 outcome: challenges ahead

Authors: Fani Chatzopoulou, Georgia Gioula, Ioannis Kioumis, Dimitris Chatzidimitriou, Maria Exindari

Published in: Medical Microbiology and Immunology | Issue 5/2019

Abstract

Influenza remains an important threat for human health, despite the extensive study of influenza viruses and the production of effective vaccines. In contrast to virus genetics determinants, host genetic factors with clinical impact remained unexplored until recently. The association between three single nucleotide polymorphisms (SNPs) and influenza outcome in a European population was investigated in the present study. All samples were collected during the influenza A(H1N1)pdm09 post-pandemic period 2010–11 and a sufficient number of severe and fatal cases was included. Host genomic DNA was isolated from pharyngeal samples of 110 patients from northern Greece with severe (n = 59) or mild (n = 51) influenza A(H1N1)pdm09 disease, at baseline, and the genotype of CD55 rs2564978, C1QBP rs3786054 and FCGR2A rs1801274 SNPs was investigated. Our findings suggest a relationship between the two complement-related SNPs, namely, the rare TT genotype of CD55 and the rare AA genotype of C1QBP with increased death risk. No significant differences were observed for FCGR2A genotypes neither with fatality nor disease severity. Additional large-scale genetic association studies are necessary for the identification of reliable host genetic risk factors associated with influenza A(H1N1)pdm09 outcome. Prophylactic intervention of additional high-risk populations, according to their genetic profile, will be a key achievement for the fight against influenza viruses.

WHO (2014) World health organization: influenza (seasonal). http://www.who.int/mediacentre/factsheets/fs211/en/. Accessed Sep 2017

Neumann G, Noda T, Kawaoka Y (2009) Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459(7249):931–939. https://doi.org/10.1038/nature08157 CrossRefPubMedPubMedCentral

CDC (2010) Deaths and hospitalizations related to 2009 pandemic influenza A (H1N1)—Greece, May 2009–February 2010. MMWR Morb Mortal Wkly Rep 59(22):682–686

Athanasiou M, Lytras T, Spala G, Triantafyllou E, Gkolfinopoulou K, Theocharopoulos G, Patrinos S, Danis K, Detsis M, Tsiodras S, Bonovas S, Panagiotopoulos T (2010) Fatal cases associated with pandemic influenza A (H1N1) reported in Greece. PLoS Curr 2:RRN1194. https://doi.org/10.1371/currents.RRN1194 CrossRefPubMedPubMedCentral

Athanasiou M, Baka A, Andreopoulou A, Spala G, Karageorgou K, Kostopoulos L, Patrinos S, Sideroglou T, Triantafyllou E, Mentis A, Malisiovas N, Lytras T, Tsiodras S, Panagiotopoulos T, Bonovas S (2011) Influenza surveillance during the post-pandemic influenza 2010/11 season in Greece, 04 October 2010–22 May 2011. Euro Surveill. https://doi.org/10.2807/ese.16.44.20004-en CrossRefPubMed

Melidou A, Exindari M, Gioula G, Malisiovas N (2013) Severity of the two post-pandemic influenza seasons 2010–11 and 2011–12 in Northern Greece. Hippokratia 17(2):150–152PubMedPubMedCentral

Hayward AC, Fragaszy EB, Bermingham A, Wang L, Copas A, Edmunds WJ, Ferguson N, Goonetilleke N, Harvey G, Kovar J, Lim MS, McMichael A, Millett ER, Nguyen-Van-Tam JS, Nazareth I, Pebody R, Tabassum F, Watson JM, Wurie FB, Johnson AM, Zambon M, Flu Watch G (2014) Comparative community burden and severity of seasonal and pandemic influenza: results of the flu watch cohort study. Lancet Respir Med 2(6):445–454. https://doi.org/10.1016/S2213-2600(14)70034-7 CrossRefPubMed

Cheng VC, To KK, Tse H, Hung IF, Yuen KY (2012) Two years after pandemic influenza A/2009/H1N1: what have we learned? Clin Microbiol Rev 25(2):223–263. https://doi.org/10.1128/CMR.05012-11 CrossRefPubMedPubMedCentral

CDC (2017) People at high risk of developing flu-related complications. Centers for disease control and prevention. https://www.cdc.gov/flu/about/disease/high_risk.htm. Accessed Sep 2017

10.

van Zyl G (2006) Laboratory Findings. In: Kamps B, Hoffmann C, Preiser W (eds) Influenza report 2006. Flying Publisher, Paris, pp 150–159

11.

Dawood FS, Iuliano AD, Reed C, Meltzer MI, Shay DK, Cheng PY, Bandaranayake D, Breiman RF, Brooks WA, Buchy P, Feikin DR, Fowler KB, Gordon A, Hien NT, Horby P, Huang QS, Katz MA, Krishnan A, Lal R, Montgomery JM, Molbak K, Pebody R, Presanis AM, Razuri H, Steens A, Tinoco YO, Wallinga J, Yu H, Vong S, Bresee J, Widdowson MA (2012) Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 12(9):687–695. https://doi.org/10.1016/S1473-3099(12)70121-4 CrossRefPubMed

12.

Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM (2009) Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 361(20):1945–1952. https://doi.org/10.1056/NEJMoa0906453 CrossRefPubMed

13.

Horby P, Nguyen NY, Dunstan SJ, Baillie JK (2013) An updated systematic review of the role of host genetics in susceptibility to influenza. Influenza Other Respir Viruses 7 Suppl 2:37–41. https://doi.org/10.1111/irv.12079 CrossRefPubMedPubMedCentral

14.

Horby P, Nguyen NY, Dunstan SJ, Baillie JK (2012) The role of host genetics in susceptibility to influenza: a systematic review. PLoS One 7(3):e33180. https://doi.org/10.1371/journal.pone.0033180 CrossRefPubMedPubMedCentral

15.

Ribeiro AF, Pellini AC, Kitagawa BY, Marques D, Madalosso G, de Cassia Nogueira Figueira G, Fred J, Albernaz RK, Carvalhanas TR, Zanetta DM (2015) Risk factors for death from Influenza A(H1N1)pdm09, state of Sao Paulo, Brazil, 2009. PLoS One 10(3):e0118772. https://doi.org/10.1371/journal.pone.0118772 CrossRefPubMedPubMedCentral

16.

Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA (2008) Evidence for a heritable predisposition to death due to influenza. J Infect Dis 197(1):18–24. https://doi.org/10.1086/524064 CrossRefPubMed

17.

Gottfredsson M, Halldorsson BV, Jonsson S, Kristjansson M, Kristjansson K, Kristinsson KG, Love A, Blondal T, Viboud C, Thorvaldsson S, Helgason A, Gulcher JR, Stefansson K, Jonsdottir I (2008) Lessons from the past: familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918. Proc Natl Acad Sci USA 105(4):1303–1308. https://doi.org/10.1073/pnas.0707659105 CrossRefPubMed

18.

Li Q, Brass AL, Ng A, Hu Z, Xavier RJ, Liang TJ, Elledge SJ (2009) A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc Natl Acad Sci USA 106(38):16410–16415. https://doi.org/10.1073/pnas.0907439106 CrossRefPubMed

19.

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139(7):1243–1254. https://doi.org/10.1016/j.cell.2009.12.017 CrossRefPubMedPubMedCentral

20.

König R, Stertz S, Zhou Y, Inoue A, Hoffmann HH, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y, Gao Q, Andrews SE, Bandyopadhyay S, De Jesus P, Tu BP, Pache L, Shih C, Orth A, Bonamy G, Miraglia L, Ideker T, Garcia-Sastre A, Young JA, Palese P, Shaw ML, Chanda SK (2010) Human host factors required for influenza virus replication. Nature 463(7282):813–817. https://doi.org/10.1038/nature08699 CrossRefPubMedPubMedCentral

21.

To KK, Zhou J, Chan JF, Yuen KY (2015) Host genes and influenza pathogenesis in humans: an emerging paradigm. Curr Opin Virol 14:7–15. https://doi.org/10.1016/j.coviro.2015.04.010 CrossRefPubMed

22.

Zuniga J, Buendia-Roldan I, Zhao Y, Jimenez L, Torres D, Romo J, Ramirez G, Cruz A, Vargas-Alarcon G, Sheu CC, Chen F, Su L, Tager AM, Pardo A, Selman M, Christiani DC (2012) Genetic variants associated with severe pneumonia in A/H1N1 influenza infection. Eur Respir J 39(3):604–610. https://doi.org/10.1183/09031936.00020611 CrossRefPubMed

23.

Lin TY, Brass AL (2013) Host genetic determinants of influenza pathogenicity. Curr Opin Virol 3(5):531–536. https://doi.org/10.1016/j.coviro.2013.07.005 CrossRefPubMedPubMedCentral

24.

Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D, International SNPMWG (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409(6822):928–933. https://doi.org/10.1038/35057149 CrossRefPubMed

25.

Wang DG, Fan JB, Siao CJ, Berno A, Young P, Sapolsky R, Ghandour G, Perkins N, Winchester E, Spencer J, Kruglyak L, Stein L, Hsie L, Topaloglou T, Hubbell E, Robinson E, Mittmann M, Morris MS, Shen N, Kilburn D, Rioux J, Nusbaum C, Rozen S, Hudson TJ, Lipshutz R, Chee M, Lander ES (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280(5366):1077–1082CrossRefPubMed

26.

International HapMap C, Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Peltonen L, Dermitzakis E, Bonnen PE, Altshuler DM, Gibbs RA, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Yu F, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Gibbs RA, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, Nemesh J, Dermitzakis E, Keinan A, Montgomery SB, Pollack S, Price AL, Soranzo N, Bonnen PE, Gibbs RA, Gonzaga-Jauregui C, Keinan A, Price AL, Yu F, Anttila V, Brodeur W, Daly MJ, Leslie S, McVean G, Moutsianas L, Nguyen H, Schaffner SF, Zhang Q, Ghori MJ, McGinnis R, McLaren W, Pollack S, Price AL, Schaffner SF, Takeuchi F, Grossman SR, Shlyakhter I, Hostetter EB, Sabeti PC, Adebamowo CA, Foster MW, Gordon DR, Licinio J, Manca MC, Marshall PA, Matsuda I, Ngare D, Wang VO, Reddy D, Rotimi CN, Royal CD, Sharp RR, Zeng C, Brooks LD, McEwen JE (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467(7311):52–58. https://doi.org/10.1038/nature09298 CrossRef

27.

Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB, Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P (2012) IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484(7395):519–523. https://doi.org/10.1038/nature10921 CrossRefPubMedPubMedCentral

28.

Antonopoulou A, Baziaka F, Tsaganos T, Raftogiannis M, Koutoukas P, Spyridaki A, Mouktaroudi M, Kotsaki A, Savva A, Georgitsi M, Giamarellos-Bourboulis EJ (2012) Role of tumor necrosis factor gene single nucleotide polymorphisms in the natural course of 2009 influenza A H1N1 virus infection. Int J Infect Dis 16(3):e204–e208. https://doi.org/10.1016/j.ijid.2011.11.012 CrossRefPubMed

29.

Zhou J, To KK, Dong H, Cheng ZS, Lau CC, Poon VK, Fan YH, Song YQ, Tse H, Chan KH, Zheng BJ, Zhao GP, Yuen KY (2012) A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J Infect Dis 206(4):495–503. https://doi.org/10.1093/infdis/jis378 CrossRefPubMed

30.

Maestri A, Sortica VA, Tovo-Rodrigues L, Santos MC, Barbagelata L, Moraes MR, Alencar de Mello W, Gusmao L, Sousa RC, Emanuel Batista Dos Santos S (2015) Siaalpha2-3Galbeta1- receptor genetic variants are associated with influenza A(H1N1)pdm09 severity. PLoS One 10(10):e0139681. https://doi.org/10.1371/journal.pone.0139681 CrossRefPubMedPubMedCentral

31.

Morales-Garcia G, Falfan-Valencia R, Garcia-Ramirez RA, Camarena A, Ramirez-Venegas A, Castillejos-Lopez M, Perez-Rodriguez M, Gonzalez-Bonilla C, Grajales-Muniz C, Borja-Aburto V, Mejia-Arangure JM (2012) Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study. BMC Infect Dis 12:299. https://doi.org/10.1186/1471-2334-12-299 CrossRefPubMedPubMedCentral

32.

Zhang Y, Zhang Z, Cao L, Lin J, Yang Z, Zhang X (2017) A common CD55 rs2564978 variant is associated with the susceptibility of non-small cell lung cancer. Oncotarget 8(4):6216–6221. https://doi.org/10.18632/oncotarget.14053 CrossRefPubMed

33.

Kishore U, Reid KB (2000) C1q: structure, function, and receptors. Immunopharmacology 49(1–2):159–170CrossRefPubMed

34.

Bermejo-Martin JF, Martin-Loeches I, Rello J, Anton A, Almansa R, Xu L, Lopez-Campos G, Pumarola T, Ran L, Ramirez P, Banner D, Ng DC, Socias L, Loza A, Andaluz D, Maravi E, Gomez-Sanchez MJ, Gordon M, Gallegos MC, Fernandez V, Aldunate S, Leon C, Merino P, Blanco J, Martin-Sanchez F, Rico L, Varillas D, Iglesias V, Marcos MA, Gandia F, Bobillo F, Nogueira B, Rojo S, Resino S, Castro C, Ortiz de Lejarazu R, Kelvin D (2010) Host adaptive immunity deficiency in severe pandemic influenza. Crit Care 14(5):R167. https://doi.org/10.1186/cc9259 CrossRefPubMedPubMedCentral

35.

CDC (2009) CDC protocol of realtime RTPCR for swine influenza A(H1N1). World health organisation. http://www.who.int/csr/resources/publications/swineflu/CDCrealtimeRTPCRprotocol_20090428.pdf. Accessed Sep 2017

36.

Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG,, American Thoracic S (2007) Infectious diseases society of A. infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(Suppl 2):S27–S72. https://doi.org/10.1086/511159 CrossRef

37.

Bretz F, Hothorn T, Westfall P (2010) Multiple comparisons using R. Chapman and Hall/CRC, Boca Raton

38.

WHO (2009) Pandemic (H1N1) 2009—update 109. WHO global alert and response [online]. http://www.who.int/csr/don/2010_07_16/en/index.html Accessed Sep 2017

39.

Garcia-Etxebarria K, Bracho MA, Galan JC, Pumarola T, Castilla J, Ortiz de Lejarazu R, Rodriguez-Dominguez M, Quintela I, Bonet N, Garcia-Garcera M, Dominguez A, Gonzalez-Candelas F, Calafell F, Cases C, Controls in Pandemic Influenza Working G (2015) No major host genetic risk factor contributed to A(H1N1)2009 influenza severity. PLoS One 10(9):e0135983. https://doi.org/10.1371/journal.pone.0135983 CrossRefPubMedPubMedCentral

40.

Lee N, Cao B, Ke C, Lu H, Hu Y, Tam CHT, Ma RCW, Guan D, Zhu Z, Li H, Lin M, Wong RYK, Yung IMH, Hung TN, Kwok K, Horby P, Hui DSC, Chan MCW, Chan PKS (2017) IFITM3, TLR3, and CD55 gene SNPs and cumulative genetic risks for severe outcomes in Chinese patients with H7N9/H1N1pdm09 influenza. J Infect Dis 216(1):97–104. https://doi.org/10.1093/infdis/jix235 CrossRefPubMed

41.

Stoermer KA, Morrison TE (2011) Complement and viral pathogenesis. Virology 411(2):362–373. https://doi.org/10.1016/j.virol.2010.12.045 CrossRefPubMedPubMedCentral

42.

Clark MR, Stuart SG, Kimberly RP, Ory PA, Goldstein IM (1991) A single amino acid distinguishes the high-responder from the low-responder form of Fc receptor II on human monocytes. Eur J Immunol 21(8):1911–1916. https://doi.org/10.1002/eji.1830210820 CrossRefPubMed

43.

van Sorge NM, van der Pol WL, van de Winkel JG (2003) FcgammaR polymorphisms: Implications for function, disease susceptibility and immunotherapy. Tissue Antigens 61(3):189–202CrossRefPubMed

44.

Maestri A, Sortica VA, Ferreira DL, de Almeida Ferreira J, Amador MA, de Mello WA, Santos SE, Sousa RC (2016) The His131Arg substitution in the FCGR2A gene (rs1801274) is not associated with the severity of influenza A(H1N1)pdm09 infection. BMC Res Notes 9:296. https://doi.org/10.1186/s13104-016-2096-1 CrossRefPubMedPubMedCentral

Title: Identification of complement-related host genetic risk factors associated with influenza A(H1N1)pdm09 outcome: challenges ahead
Authors: Fani Chatzopoulou
Georgia Gioula
Ioannis Kioumis
Dimitris Chatzidimitriou
Maria Exindari
Publication date: 01-10-2019
Publisher: Springer Berlin Heidelberg
Published in: Medical Microbiology and Immunology / Issue 5/2019
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-018-0567-9

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