Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome

Liu, Zhengwen; Gao, Maicang; Han, Qunying; Lou, Sai; Fang, Jie

doi:10.1016/j.humimm.2009.03.009

Cited by 21 publications

(20 citation statements)

References 46 publications

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“…Pathogenic hantavirus binding to inactive ␣ v ␤ 3 integrins is consistent with the selective inhibitory effect of hantaviruses on ␣ v ␤ 3 function and endothelial cell permeability (14,15,38). Although the mechanism of hantavirus induced vascular permeability has yet to be defined, there is a clear role for ␤ 3 integrin dysfunction in vascular permeability deficits (5,6,22,29,39,40,51) which make an understanding of hantavirus interactions with ␤ 3 subunits important for both entry and disease processes.…”

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confidence: 62%

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Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain

Matthys

Gorbunova

Gavrilovskaya

et al. 2010

J Virol

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Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans and Syrian hamsters.Human ␣ v ␤ 3 integrins are receptors for several pathogenic hantaviruses, and the function of ␣ v ␤ 3 integrins on endothelial cells suggests a role for ␣ v ␤ 3 in hantavirus directed vascular permeability. We determined here that ANDV infection of human endothelial cells or Syrian hamster-derived BHK-21 cells was selectively inhibited by the high-affinity ␣ v ␤ 3 integrin ligand vitronectin and by antibodies to ␣ v ␤ 3 integrins. Further, antibodies to the ␤ 3 integrin PSI domain, as well as PSI domain polypeptides derived from human and Syrian hamster ␤ 3 subunits, but not murine or bovine ␤ 3 , inhibited ANDV infection of both BHK-21 and human endothelial cells. These findings suggest that ANDV interacts with ␤ 3 subunits through PSI domain residues conserved in both Syrian hamster and human ␤ 3 integrins. Sequencing the Syrian hamster ␤ 3 integrin PSI domain revealed eight differences between Syrian hamster and human ␤ 3 integrins. Analysis of residues within the PSI domains of human, Syrian hamster, murine, and bovine ␤ 3 integrins identified unique proline substitutions at residues 32 and 33 of murine and bovine PSI domains that could determine ANDV recognition. Mutagenizing the human ␤ 3 PSI domain to contain the L33P substitution present in bovine ␤ 3 integrin abolished the ability of the PSI domain to inhibit ANDV infectivity. Conversely, mutagenizing either the bovine PSI domain, P33L, or the murine PSI domain, S32P, to the residue present human ␤ 3 permitted PSI mutants to inhibit ANDV infection. Similarly, CHO cells transfected with the full-length bovine ␤ 3 integrin containing the P33L mutation permitted infection by ANDV. These findings indicate that human and Syrian hamster ␣ v ␤ 3 integrins are key receptors for ANDV and that specific residues within the ␤ 3 integrin PSI domain are required for ANDV infection. Since L33P is a naturally occurring human ␤ 3 polymorphism, these findings further suggest the importance of specific ␤ 3 integrin residues in hantavirus infection. These findings rationalize determining the role of ␤ 3 integrins in hantavirus pathogenesis in the Syrian hamster model.

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confidence: 62%

“…Unfortunately, there are no patient data available on the role of the HPA-1a/1b polymorphism on hantavirus infection or disease. One study has indicated that a polymorphism in the HPA-3b allele (I843S) of ␣ IIb ␤ 3 integrins results in more severe clinical HFRS disease (29). However, since only 1% of the Asian population is homozygous for the FIG.…”

mentioning

confidence: 99%

Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain

Matthys

Gorbunova

Gavrilovskaya

et al. 2010

J Virol

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“…[32] Our findings are similar to the only previous study on hantavirus infection and GP IIIa polymorphism which found that the HPA-1 polymorphism does not associate with disease severity. [7]…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Laine¹,

Joutsi‐Korhonen²,

Mäkelä³

et al. 2012

Thrombosis Research

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Introduction Puumala virus (PUUV) infection is a viral hemorrhagic fever with renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of renal function. We aimed to assess whether genetic polymorphisms of platelet antigens together with those of von Willebrand factor (VWF) and plasminogen activator inhibitor (PAI-1) correlate with disease severity. Patients and methods 172 consecutive hospital-treated patients with serologically confirmed acute PUUV infection were included. Platelet glycoprotein (GP) IIIa T>C (rs5918), GP Ia T>C (rs1126643), GP Ib C>T (rs6065), GP VI T>C (rs1613662), VWF A>G (rs1063856) and PAI-1 A>G (rs2227631) were genotyped. The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed. Results PAI-1 G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 μmol/l, range 60–1499 μmol/l vs. median 122 μmol/l, range 51–1156 μmol/l, p=0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 μmol/l, 204 μmol/l and 122 μmol/l, respectively, p=0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels during PUUV infection. The minor C-allele of GP Ia associated with lower platelet counts (median 44×109/l, range 20–90×109/l vs median 64×109/l, range 3–238×109/l; p=0.02). Conclusions Polymorphism of PAI-1, a major regulator of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV-HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower platelet count.

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“…Polymorphisms of platelet glycoprotein IIb/IIIa alloatigen ( HPA1/HPA3 ) have been investigated and HPA-3, but not HPA-1, was more frequent in Chinese patients with severe than mild HFRS [59]. …”

Section: Impact Of Genetic Factors In Human Hantavirus Infectionsmentioning

confidence: 99%

“…Hence, HLA-DRB1*09 and HLA-B*46–DRB1*09 were more common in Chinese patients with HTNV-induced HFRS than in healthy individuals [48,68]. Moreover, non-carriage of the interleukin-1 receptor antagonist ( IL-1RA ) allele 2 and the IL-1b (−511) allele 2 [58] as well as HPA-3 b allele [59] were more frequent in HFRS patients than in seronegative controls. These alleles/haplotypes could thus be identified as genetic risk factors associated with the susceptibility to hantavirus infections [59].…”

Section: Impact Of Genetic Factors In Human Hantavirus Infectionsmentioning

confidence: 99%

Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

Charbonnel

Pagès

Sironen

et al. 2014

Viruses

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We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives.

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Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome

Cited by 21 publications

References 46 publications

Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain

Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

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Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome

Cited by 21 publications

References 46 publications

Andes Virus Recognition of Human and Syrian Hamster β 3 Integrins Is Determined by an L33P Substitution in the PSI Domain

Andes Virus Recognition of Human and Syrian Hamster β 3 Integrins Is Determined by an L33P Substitution in the PSI Domain

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

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Product

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Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain

Andes Virus Recognition of Human and Syrian Hamster β ₃ Integrins Is Determined by an L33P Substitution in the PSI Domain