1887

Abstract

Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50 % of fatal cases, 25–50 % of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency ( mutation, a 32 bp deletion in the gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for and evaluated its correlation with patient mortality. patients (17.4 %) showed a higher mortality rate than WT individuals (4.7 %;  = 0.021), which indicates that patients are at higher risk than the normal population of a fatal outcome in influenza infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000165
2015-08-01
2019-09-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/8/2074.html?itemId=/content/journal/jgv/10.1099/vir.0.000165&mimeType=html&fmt=ahah

References

  1. Antonopoulou A., Baziaka F., Tsaganos T., Raftogiannis M., Koutoukas P., Spyridaki A., Mouktaroudi M., Kotsaki A., Savva A., other authors. ( 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: e204–e208 [CrossRef] [PubMed].
    [Google Scholar]
  2. Aranda-Romo S., Garcia-Sepulveda C.A., Comas-García A., Lovato-Salas F., Salgado-Bustamante M., Gómez-Gómez A., Noyola D.E.. ( 2012;). Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza infections. Immunogenetics 64: 653–662 [CrossRef] [PubMed].
    [Google Scholar]
  3. Benkirane M., Jin D.Y., Chun R.F., Koup R.A., Jeang K.T.. ( 1997;). Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5Δ32. J Biol Chem 272: 30603–30606 [CrossRef] [PubMed].
    [Google Scholar]
  4. Dawson T.C., Beck M.A., Kuziel W.A., Henderson F., Maeda N.. ( 2000;). Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am J Pathol 156: 1951–1959 [CrossRef] [PubMed].
    [Google Scholar]
  5. Dean M., Carrington M., Winkler C., Huttley G.A., Smith M.W., Allikmets R., Goedert J.J., Buchbinder S.P., Vittinghoff E., other authors. ( 1996;). Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273: 1856–1862 [CrossRef] [PubMed].
    [Google Scholar]
  6. Downer M.V., Hodge T., Smith D.K., Qari S.H., Schuman P., Mayer K.H., Klein R.S., Vlahov D., Gardner L.I., McNicholl J.M.. ( 2002;). Regional variation in CCR5-Δ32 gene distribution among women from the US HIV Epidemiology Research Study (HERS). Genes Immun 3: 295–298 [CrossRef] [PubMed].
    [Google Scholar]
  7. Esposito S., Molteni C.G., Giliani S., Mazza C., Scala A., Tagliaferri L., Pelucchi C., Fossali E., Plebani A., Principi N.. ( 2012;). Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children. Virol J 9: 270 [CrossRef] [PubMed].
    [Google Scholar]
  8. Everitt A.R., Clare S., Pertel T., John S.P., Wash R.S., Smith S.E., Chin C.R., Feeley E.M., Sims J.S., other authors. ( 2012;). IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484: 519–523 [CrossRef] [PubMed].
    [Google Scholar]
  9. Falagas M.E., Koletsi P.K., Baskouta E., Rafailidis P.I., Dimopoulos G., Karageorgopoulos D.E.. ( 2011;). Pandemic A(H1N1) 2009 influenza: review of the Southern Hemisphere experience. Epidemiol Infect 139: 27–40 [CrossRef] [PubMed].
    [Google Scholar]
  10. Keynan Y., Juno J., Meyers A., Ball T.B., Kumar A., Rubinstein E., Fowke K.R.. ( 2010;). Chemokine receptor 5 Δ32 allele in patients with severe pandemic (H1N1) 2009. Emerg Infect Dis 16: 1621–1622 [CrossRef] [PubMed].
    [Google Scholar]
  11. Kindberg E., Mickiene A., Ax C., Akerlind B., Vene S., Lindquist L., Lundkvist A., Svensson L.. ( 2008;). A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis. J Infect Dis 197: 266–269 [CrossRef] [PubMed].
    [Google Scholar]
  12. Kohlmeier J.E., Miller S.C., Smith J., Lu B., Gerard C., Cookenham T., Roberts A.D., Woodland D.L.. ( 2008;). The chemokine receptor CCR5 plays a key role in the early memory CD8+T cell response to respiratory virus infections. Immunity 29: 101–113 [CrossRef] [PubMed].
    [Google Scholar]
  13. Libert F., Cochaux P., Beckman G., Samson M., Aksenova M., Cao A., Czeizel A., Claustres M., de la Rúa C., other authors. ( 1998;). The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. Hum Mol Genet 7: 399–406 [CrossRef] [PubMed].
    [Google Scholar]
  14. Lim J.K., Louie C.Y., Glaser C., Jean C., Johnson B., Johnson H., McDermott D.H., Murphy P.M.. ( 2008;). Genetic deficiency of chemokine receptor CCR5 is a strong risk factor for symptomatic West Nile virus infection: a meta-analysis of 4 cohorts in the US epidemic. J Infect Dis 197: 262–265 [CrossRef] [PubMed].
    [Google Scholar]
  15. Liu R., Paxton W.A., Choe S., Ceradini D., Martin S.R., Horuk R., MacDonald M.E., Stuhlmann H., Koup R.A., Landau N.R.. ( 1996;). Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86: 367–377 [CrossRef] [PubMed].
    [Google Scholar]
  16. Louie J.K., Acosta M., Samuel M.C., Schechter R., Vugia D.J., Harriman K., Matyas B.T., California Pandemic (H1N1) Working Group. ( 2011;). A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 52: 301–312 [CrossRef] [PubMed].
    [Google Scholar]
  17. Neumann G., Noda T., Kawaoka Y.. ( 2009;). Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459: 931–939 [CrossRef] [PubMed].
    [Google Scholar]
  18. Rodriguez A., Falcon A., Cuevas M.T., Pozo F., Guerra S., García-Barreno B., Martinez-Orellana P., Pérez-Breña P., Montoya M., other authors. ( 2013;). Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case. PLOS One 8: e53515 [CrossRef] [PubMed].
    [Google Scholar]
  19. Rodríguez-Rodríguez L., González-Juanatey C., García-Bermúdez M., Vázquez-Rodríguez T.R., Miranda-Filloy J.A., Fernández-Gutiérrez B., Llorca J., Martin J., González-Gay M.A.. ( 2011;). CCR5Δ32 variant and cardiovascular disease in patients with rheumatoid arthritis: a cohort study. Arthritis Res Ther 13: R133 [CrossRef] [PubMed].
    [Google Scholar]
  20. Samson M., Libert F., Doranz B.J., Rucker J., Liesnard C., Farber C.M., Saragosti S., Lapoumeroulie C., Cognaux J., other authors. ( 1996;). Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382: 722–725 [CrossRef] [PubMed].
    [Google Scholar]
  21. Singanayagam A., Singanayagam A., Wood V., Chalmers J.D.. ( 2011;). Factors associated with severe illness in pandemic 2009 influenza a (H1N1) infection: implications for triage in primary and secondary care. J Infect 63: 243–251 [CrossRef] [PubMed].
    [Google Scholar]
  22. Sironi M., Cagliani R., Pontremoli C., Rossi M., Migliorino G., Clerici M., Gori A.. ( 2014;). The CCR5Δ32 allele is not a major predisposing factor for severe H1N1pdm09 infection. BMC Res Notes 7: 504 [CrossRef] [PubMed].
    [Google Scholar]
  23. Zhou J., To K.K., Dong H., Cheng Z.S., Lau C.C., Poon V.K., Fan Y.H., Song Y.Q., Tse H., other authors. ( 2012;). A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection. J Infect Dis 206: 495–503 [CrossRef] [PubMed].
    [Google Scholar]
  24. Zimmerman P.A., Buckler-White A., Alkhatib G., Spalding T., Kubofcik J., Combadiere C., Weissman D., Cohen O., Rubbert A., other authors. ( 1997;). Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk. Mol Med 3: 23–36 [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000165
Loading
/content/journal/jgv/10.1099/vir.0.000165
Loading

Data & Media loading...

Supplementary Data



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error