Susceptibilidad genética a hantavirus Andes: Asociación entre la expresión clínica de la infección y alelos del sistema HLA en pacientes chilenos

Ferrer, Pablo; G, Marcela Ferrés; M, Paula Godoy; Culza, Analla; C, Claudia Marco; H., Constanza Castillo; C, María Elena Umaña; E, Francisco Rothhammer; R, Elena Llop

doi:10.4067/s0716-10182007000500001

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…These studies have established a connection between several HLA alleles and haplotypes and the severe course of PUUV. (6-9) Our study is the first GWAS on PUUV infection and we strongly confirm the association to HLA region with two independent variants, one located in HLA class I region in between HLA-DRB1 and HLA-DQA1 genes and the other in HLA class II region closest to the HLA-C gene. The association at the ERAP1 locus is a novel finding in the context of PUUV infection yet the gene has previously been linked to various autoimmune disorders such as ankylosing spondylitis and psoriasis, as well as infections including hepatitis C, influenza, and HIV.…”

Section: Discussionsupporting

confidence: 75%

“…Small case-control studies have identified several HLA alleles and haplotypes associated with severe disease, although the findings vary between studies. (6)(7)(8)(9) We utilized data from 520,210 individuals participating in the FinnGen project to explore the biological mechanisms behind PUUV infection. With International Classification of Diseases (ICD) code-based case definition, we identified 3,650 cases of PUUV infection diagnosed between 1995 and 2023.…”

Section: Introductionmentioning

confidence: 99%

“…Small case-control studies have identified several HLA alleles and haplotypes associated with severe disease, although the findings vary between studies. (6-9)…”

Section: Introductionmentioning

confidence: 99%

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Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

Haapaniemi,

Strausz,

Tervi

et al. 2024

Preprint

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Puumala virus (PUUV) infections can cause severe illnesses such as Hemorrhagic Fever with Renal Syndrome in humans. However, human genetic risk factors contributing to disease severity are still poorly understood. Our goal was to elucidate genetic factors contributing to PUUV infections and understand the biological mechanisms underlying individual vulnerability to the disease. Leveraging data from the FinnGen study, we conducted a genome-wide association study on severe Hemorrhagic Fever with Renal Syndrome caused by PUUV with 2,227 cases. We identified associations at the Human Leukocyte Antigen (HLA) locus andERAP1with severe PUUV infection. HLA molecules are canonical mediators for immune recognition and response.ERAP1facilitates immune system recognition and activation by cleaving viral proteins into smaller peptides which are presented to the immune system via HLA class I molecules. Notably, we identified that the lead variant (rs26653, OR = 0.84, p = 2.93×10-8) in theERAP1gene was a missense variant changing amino acid arginine to proline. From the HLA region, we showed independent and significant associations with both HLA class I and II genes. Furthermore, we showed independent associations with nine HLA alleles and severe PUUV infection using conditional HLA fine-mapping. The strongest association was found with theHLA-C*07:01allele (OR = 1.5, p = 4.0×10−24) followed by signals atHLA-B*13:02, HLA-DRB1*01:01, andHLA-DRB1*11:01alleles (p<5×10−8). Our findings suggest that viral peptide processing withERAP1and antigen presentation through HLA alleles contribute to the development of severe PUUV disease.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

Haapaniemi,

Strausz,

Tervi

et al. 2024

Preprint

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“…In accordance with this supposition, in another study carried out in Slovenia, higher frequencies of the HLA‐B*35 allele were found among HFRS patients infected with Dobrava virus (DOBV) with a fatal outcome [Korva et al, ]. However, a previous study carried out with Chilean individuals infected with ANDV showed that the HLA‐B*35 allele was more frequent among patients with mild disease (without respiratory failure and shock) than those with severe disease, but without statistical significance [Ferrer et al, ]. Furthermore, another study demonstrated that strong HLA‐B*35‐restricted memory T cell responses to ANDV were associated with mild, rather than severe disease, outcome [Manigold et al, ].…”

Section: Discussionmentioning

confidence: 90%

“…Hantavirus cardiopulmonary syndrome is associated with acute thrombocytopenia and changes in vascular permeability that can cause capillary leaking syndrome, leading to inflammatory pulmonary edema, myocarditis, and cardiogenic shock [Saggioro et al, ; Borges and Figueiredo, ]. Several studies have suggested that host genetic polymorphisms may influence the clinical outcome of hantavirus infection, resulting in milder or more severe illness [Mäkelä et al, ; Kilpatrick et al, ; Ferrer et al, ; Wang et al, ; Borges et al, ; Korva et al, ; Laine et al, ]. Furthermore, serological surveys have demonstrated anti‐hantavirus antibodies in individuals without cardiopulmonary illness history [Campos et al, ; Pereira et al, ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in human leukocyte antigens, human platelet antigens, and cytokine genes in hantavirus cardiopulmonary syndrome patients from Ribeirão Preto, Brazil

Borges

Donadi

Figueiredo

et al. 2013

Journal of Medical Virology

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Hantavirus cardiopulmonary syndrome is a severe human disease associated with hantavirus infection. The clinical course of illness varies greatly among individuals, possibly due to viral and immunological elements and the influence of host genetic factors on clinical outcome. As the magnitude of immune activation has been associated with disease severity, polymorphisms in genes involved in the immune response that may affect the development of this syndrome were investigated. Polymorphisms in the TGF-β, IL-10, IL-6, and IFN-γ genes, human leukocyte antigens (HLA), and human platelet alloantigens (HPA) genes were investigated in 122 patients with Araraquara virus infection from Ribeirão Preto, Brazil. Patients were divided into two groups: hantavirus cardiopulmonary syndrome (HCPS group; n = 26) and hantavirus seropositive only (n = 96). The frequencies of HLA alleles, cytokines and platelet antigen genotypes were evaluated in both groups and compared to a control group. The data demonstrated no significant influence of the HLA alleles, HPA, IL-6, and IL-10 genotypes on susceptibility to hantavirus infection. However, the hantavirus seropositive group presented a significantly higher frequency of a polymorphism associated with a high IFN-γ production than the HCPS group. In addition, a genotype associated with high TGF-β production was found more frequently in individuals infected with hantavirus than in the control group. This phenotype was associated with a less intense thrombocytopenia in the HCPS group and may be protective against the most severe form of hantavirus disease. More studies are required to quantify further the influence of the high TGF-β producer phenotype on the outcome of hantavirus infection.

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Hantavirus Genetic Diversity

Blasdell

Hentonnen²,

Buchy

2011

New Frontiers of Molecular Epidemiology of Infectious Diseases

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Susceptibilidad genética a hantavirus Andes: Asociación entre la expresión clínica de la infección y alelos del sistema HLA en pacientes chilenos

Cited by 14 publications

References 45 publications

Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

Polymorphisms in human leukocyte antigens, human platelet antigens, and cytokine genes in hantavirus cardiopulmonary syndrome patients from Ribeirão Preto, Brazil

Hantavirus Genetic Diversity

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