IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza

Lee, Nelson; Cao, Bin; Ke, Changwen; Lu, Hongzhou; Hu, Yunwen; Tam, Claudia H.T.; Wan, Ronald Ching; Guan, Dawei; Zhu, Zhaoqin; Li, Hui; Lin, Mulei; Wong, Ricky W.K.; Yung, Irene M. H.; Hung, T. F.; Kwok, Ka‐li; Horby, Peter; Hui, David Shu Cheong; Chan, Michael; Chan, Paul Kay Sheung

doi:10.1093/infdis/jix235

Cited by 55 publications

(71 citation statements)

References 44 publications

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“…In addition, the CC genotype was estimated to confer a six-fold increased risk for severe infection than the CT and TT genotypes [120], reinforcing the idea that IFITM3 is a factor affecting human IAV disease [121]. In another study, over-representation of the IFITM3 CC genotype was detected among fatal cases of Chinese patients infected with IAV pH1N1 and H7N9 viruses [100], and in a more general study, including twelve studies published before February 2018 with more than 16,000 subjects, revealed increased risk of severe influenza in both the East Asian and White populations in the subjects encoding the IFITM3 CC genotype [122].…”

Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 80%

“…Therefore, patients who carry the T/T genotype may have more robust complement activation during IAV infection, resulting in enhanced inflammation and disease severity [47,79]. According to these results, the polymorphism rs2564978 in gene CD55 was linked to disease severity in adult Chinese cases of avian (H7N9) and human pH1N1 IAV in another study [100]. However, these findings need to be confirmed in bigger cohorts.…”

Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 90%

“…However, the SNP was found in significantly less proportion in children with milder disease, suggesting a link between TLR3 and IAV pathogenicity. Furthermore, in a multicenter study involving 275 adult cases of avian H7N9 and pH1N1 IAV, in mainland China and Hong Kong, the TLR3 CC rs5743313 SNP was associated with fatal cases [100].…”

Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 98%

“…[98] [99,100] RIG-I Detects dsRNA and 5 -triphosphates of the negative ssRNA IAV genome, leading to innate immune responses activation.…”

Section: Tlr-3mentioning

confidence: 99%

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Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Nogales¹,

DeDiego

2019

Pathogens

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A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness. multiple mechanisms, although there are some differences between strains. For that genome plasticity, IAV take advantage of multiple strategies, such as alternative splicing, frameshift mechanisms, and overlapping open reading frames (ORFs) [7][8][9]. In addition, the coding capability of the viral genome is extended by encoding multifunctional proteins that act at different steps during virus infection. of synthetized vRNP, ensuring that the vRNPs are available for packaging [24]. Moreover, NEP has also other functions during IAV infection, contributing to viral budding and to regulate viral RNA synthesis. NS1 is a multifunctional protein and a key viral factor that counteracts the host antiviral responses. NS1 has been shown to inhibit the production of interferon (IFN), the activity and expression of multiple interferon-induced genes (ISG) and the processing and nuclear transport of host mRNAs causing cellular shut-off [25,26]. Segment 3 of IAV also encodes two proteins, the polymerase component PA and PA-X. PA is translated directly from the PA mRNA, whereas PA-X is translated using a +1 frameshift mechanism from the same open reading frame (ORF) [9]. Synergistically with NS1, PA-X is also able to block the cellular antiviral responses by inhibiting host protein expression. Moreover, the PA-X protein has been shown to modulate host inflammation, immune responses, apoptosis, and virus pathogenesis [25][26][27][28][29][30].

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Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 80%

Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 90%

Section: Snps In Host Genes Affecting Iav Diseasementioning

confidence: 98%

“…[98] [99,100] RIG-I Detects dsRNA and 5 -triphosphates of the negative ssRNA IAV genome, leading to innate immune responses activation.…”

Section: Tlr-3mentioning

confidence: 99%

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Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Nogales¹,

DeDiego

2019

Pathogens

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“…Our current knowledge is limited with respect to possible mechanisms underlying severe outcomes with influenza infection . Standardized scoring systems will be key to the identification of virus and host factors related to severe outcomes . Validated biomarkers predicting severity will assist future physicians in tailoring therapies to their patients’ individual needs.…”

Section: Discussionmentioning

confidence: 99%

Partnering for enhanced digital surveillance of influenza‐like disease and the effect of antivirals and vaccines (PEDSIDEA)

Rath

Maltezou

Papaevangelou

et al. 2019

Influenza Resp Viruses

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Background Standardised clinical outcome measures are urgently needed for the surveillance of influenza and influenza‐like illness (ILI) based on individual patient data (IPD). Objectives We report a multicentre prospective cohort using a predefined disease severity score in routine care. Patients/Methods The Vienna Vaccine Safety initiative (ViVI) Disease Severity Score (“ViVI Score”) was made available as an android‐based mobile application to three paediatric hospitals in Berlin and Athens between 2013 and 2016. Healthcare professionals assessed ILI patients at the point of care including severity, risk factors and use of antibiotics/antivirals/vaccines. RT‐PCR for influenza A/B viruses was performed at the Hellenic Pasteur Institute and the Robert Koch Institute. PCR testing was blinded to severity scoring and vice versa. Results A total of 1615 children aged 0‐5 years (54.4% males) were assessed at the three sites. The mean age was 1.7 years (SD 1.5; range 0‐5.9). The success rate (completion of the scoring without disruption to the ER workflow) was 100%. ViVI Disease Severity Scores ranged from 0 to 35 (mean 13.72). Disease severity in the Berlin Cohort was slightly higher (mean 15.26) compared to the Athens Cohorts (mean 10.86 and 11.13). The administration of antibiotics was most prevalent in the Berlin Cohort, with 41.2% on antibiotics (predominantly cefuroxime) as opposed to only 0.5% on neuraminidase inhibitors. Overall, Risk‐adjusted ViVI Scores were significantly linked to the prescription of both, antibiotics and antivirals. Conclusions The Risk‐adjusted ViVI Score enables a precision medicine approach to managing ILI in multicentre settings. Using mobile applications, severity data will be obtained in real time with important implications for the evaluation of antiviral/vaccine use.

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Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admission

Carter

Hebbring

Liu

et al. 2017

Journal of Medical Virology

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Host response to influenza is highly variable, suggesting a potential role of host genetic variation. To investigate the host genetics of severe influenza in a targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune response genes were evaluated for association with seasonal influenza hospitalization in an adult study population with European ancestry. SNP allele and genotype frequencies were compared between hospitalized influenza patients (cases) and population controls in a case-control study that included a discovery group (26 cases and 993 controls) and two independent, validation groups (1 with 84 cases and 4076 controls; the other with 128 cases and 9187 controls). Cases and controls had similar allele frequencies for variant rs12252 in interferon-inducible transmembrane protein 3 (IFITM3) (P > 0.05), and the study did not replicate the previously reported association of rs12252 with hospitalized influenza. In the discovery group, the preliminary finding of an association with a nonsense polymorphism (rs8072510) within the schlafen family member 13 (SFLN13) gene (P = 0.0099) was not confirmed in either validation group. Neither rs12252 nor rs8072510 showed an association according to the presence of clinical risk factors for influenza complications (P > 0.05), suggesting that these factors did not modify associations between the SNPs and hospitalized influenza. No other SNPs showed a statistically significant association with hospitalized influenza. Further research is needed to identify genetic factors involved in host response to seasonal influenza infection and to assess whether rs12252, a low-frequency variant in Europeans, contributes to influenza severity in populations with European ancestry.

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IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza

Abstract: Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.

Cited by 55 publications

References 44 publications

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Partnering for enhanced digital surveillance of influenza‐like disease and the effect of antivirals and vaccines (PEDSIDEA)

Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admission

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