Dataset Information

Sia?2-3Gal?1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

ABSTRACT: Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Sia?2-3Gal?1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.

SUBMITTER: Maestri A

PROVIDER: S-EPMC4593567 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

Maestri Alvino A Sortica Vinicius Albuquerque VA Tovo-Rodrigues Luciana L Santos Mirleide Cordeiro MC Barbagelata Luana L Moraes Milene Raiol MR Alencar de Mello Wyller W Gusmão Leonor L Sousa Rita Catarina Medeiros RC Emanuel Batista Dos Santos Sidney S

PloS one 20151005 10

Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the ...[more]

PMID: 26436774

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Project description:BackgroundWhen an outbreak of a novel pathogen occurs, some of the most pressing questions from a public-health point of view relate to its transmissibility, and the probabilities of different clinical outcomes following infection, to allow an informed response. Estimates of these quantities are often based on household data due to the high potential for transmission in this setting, but typically a rich spectrum of individual-level outcomes (from uninfected to serious illness) are simplified to binary data (infected or not). We address the added benefit from retaining the heterogeneous outcome information in the case of the 2009-10 influenza pandemic, which posed particular problems for estimation of key epidemiological characteristics due to its relatively mild nature and hence low case ascertainment rates.MethodsWe use mathematical models of within-household transmission and case ascertainment, together with Bayesian statistics to estimate transmission probabilities stratified by household size, the variability of infectiousness of cases, and a set of probabilities describing case ascertainment. This novel approach was applied to data we collected from the early "containment phase" stage of the epidemic in Birmingham, England. We also conducted a comprehensive review of studies of household transmission of influenza A(H1N1)pdm09.ResultsWe find large variability in the published estimates of within-household transmissibility of influenza A(H1N1)pdm09 in both model-based studies and those reporting secondary attack rates, finding that these estimates are very sensitive to how an infected case is defined. In particular, we find that reliance on laboratory confirmation alone underestimates the true number of cases, while utilising the heterogeneous range of outcomes (based on case definitions) for household infections allows a far more comprehensive pattern of transmission to be elucidated.ConclusionsDifferences in household sizes and how cases are defined could account for an appreciable proportion of the reported variability of within-household transmissibility of influenza A(H1N1)pdm09. Retaining and statistically analysing the full spectrum of individual-level outcomes (based on case definitions) rather than taking a potentially arbitrary threshold for infection, provides much-needed additional information. In a future pandemic, our approach could be used as a real-time analysis tool to infer the true number of cases, within-household transmission rates and levels of case ascertainment.

Project description:BACKGROUND: Pandemic type A (H1N1) influenza arose in early 2009, probably in Mexico and the United States, and reappeared in North America in September for seven more months. An amino acid substitution in the hemagglutinin (HA), D222G, has been reported in a significant proportion of patients with a severe and fatal outcome. We studied the prevalence of HA222 substitutions in patients in Mexico during the second wave and its association with clinical outcome and pathogenicity in a mouse model. METHODS: The nucleotide sequences of hemagglutinin (HA) from viruses collected from 77 patients were determined including 50 severe and fatal cases and 27 ambulatory cases. Deep sequencing was done on 5 samples from severe or fatal cases in order to determine the quasispecies proportion. Weight loss and mortality due to infection with cultured influenza viruses were analyzed in a mouse model. RESULTS: Viruses from 14 out of 50 hospitalized patients (28%) had a non aspartic acid residue at the HA 222 position (nD222), while all 27 ambulatory patients had D222 (p=0.0014). G222 was detected as sole species or in coexistence with N222 and D222 in 12 patients with severe disease including 8 who died. N222 in coexistence with D222 was detected in 1 patient who died and co-occurrence of A222 and V222, together with D222, was detected in another patient who died. The patients with a nD222 residue had higher mortality (71.4%), compared to the group with only D222 (22.2%, p=0.0008). Four of the 14 viruses from hospitalized patients were cultured and intranasally infected into mice. Two viruses with G222 were lethal while a third virus, with G222, caused only mild illness in mice similar to the fourth virus that contained D222. CONCLUSIONS: We confirm the elevated incidence of HA222 (H1N1)pdm09 variants in severe disease and mortality. Both clinical and mouse infection data support the idea that nD222 mutations contribute to increased severity of disease but additional determinants in disease outcome may be present.

Project description:ObjectivesTo review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection.DesignA search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.”SettingOnly papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included.SampleWe included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included.Main outcome measuresDemographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection.ResultsThe retrieved cases were divided into two groups: the postvaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed.ConclusionsFatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.

Dataset Information

Sia?2-3Gal?1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

Publications

Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

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