Detection of the influenza A(H1N1)pdm09 virus carrying the K-15E, P83S and Q293H mutations in patients who have undergone bone marrow transplant

PLoS One. 2014 Apr 16;9(4):e94822. doi: 10.1371/journal.pone.0094822. eCollection 2014.

Abstract

The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Bone Marrow Transplantation*
  • Case-Control Studies
  • Child
  • DNA Mutational Analysis
  • Dogs
  • Female
  • Hemagglutinins, Viral / genetics
  • Host-Pathogen Interactions
  • Humans
  • Immunocompromised Host
  • Influenza A Virus, H1N1 Subtype / classification
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza, Human / pathology*
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Phylogeny
  • Polymorphism, Genetic
  • Severity of Illness Index
  • Young Adult

Substances

  • Hemagglutinins, Viral

Associated data

  • GENBANK/CY052046
  • GENBANK/CY052047
  • GENBANK/CY052048
  • GENBANK/CY052049
  • GENBANK/CY052050
  • GENBANK/CY052346
  • GENBANK/CY052347
  • GENBANK/CY052348
  • GENBANK/CY052349
  • GENBANK/CY052350
  • GENBANK/CY054283
  • GENBANK/CY060444
  • GENBANK/CY060450
  • GENBANK/CY072074
  • GENBANK/CY072076
  • GENBANK/CY072082
  • GENBANK/CY072085
  • GENBANK/CY072086
  • GENBANK/CY072087
  • GENBANK/CY072088
  • GENBANK/KC967083
  • GENBANK/KC967084
  • GENBANK/KC967085
  • GENBANK/KC967086
  • GENBANK/KC967087
  • GENBANK/KC967088
  • GENBANK/KC967089
  • GENBANK/KC967090
  • GENBANK/KJ417954
  • GENBANK/KJ417955
  • GENBANK/KJ417956
  • GENBANK/KJ417957
  • GENBANK/KJ417958
  • GENBANK/KJ417959
  • GENBANK/KJ417960
  • GENBANK/KJ417961

Grants and funding

The work was supported by Instituto Oswaldo Cruz/Fiocruz (www.ioc.fiocruz.br) and Brazilian Ministry of Health/Decit and SVS (http://portal2.saude.gov.br/sisct/?). Dr. Siqueira was supported in part by individual research grants from CNPq (www.cnpq.br). Dr. Siqueira and Souza used, in part, individual research grants from FAPERJ (www.faperj.br) and CNPq. Thanks are also due to IOC/Fiocruz for providing PCR and NFR fellowships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.