Novel Human Parechovirus from Brazil

Drexler, Jan Felix; Grywna, Klaus; Stöcker, Andreas; Almeida, Pedro Afonso de Oliveira; Ribeiro, Tereza Cristina Medrado; Eschbach-Bludau, Monika; Petersen, Nadine; Ribeiro, Hugo da Costa; Drosten, Christian

doi:10.3201/eid1502.081028

Cited by 103 publications

(62 citation statements)

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“…The results showed that four different HPeV genotypes, HPeV1 to HPeV4, were present among Thai infants and children with acute gastroenteritis, and more than a half of the strains detected belonged to HPeV1. That finding was in good agreement with the findings of previous studies, which reported that HPeV1 was predominant over other the HPeV genotypes found in patients with acute gastroenteritis (3,4,6,9).…”

Section: Discussionsupporting

confidence: 83%

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

et al. 2010

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A total of 82 fecal specimens which were known to be negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus and which were collected from infants and children with acute gastroenteritis in Chiang Mai, Thailand, from January to December 2005 were screened for human parechovirus (HPeV). HPeV was detected by reverse transcription-PCR with a primer pair that amplified the 5 untranslated region of its genome and was genotyped by sequencing of the VP1 region. HPeV was detected in 12 of 82 specimens tested, and the detection rate was found to be 14.6%. The capsid VP1 gene was successfully sequenced from nine of the HPeV strains detected. The HPeV strains studied clustered into four different genotypes, HPeV genotype 1 (HPeV1) to HPeV4, and the majority of the strains studied (five strains) belonged to HPeV1. This is the first finding of HPeV from children with acute gastroenteritis in Thailand. In addition, the diversity of the Thai HPeV strains was also noted.

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Section: Discussionsupporting

confidence: 83%

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

et al. 2010

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“…Direct involvement of ␣ v integrins in the infectious entry of HPEV1 was further confirmed by overexpression of human ␣ v ␤ 1 and ␣ v ␤ 3 integrins in Chinese hamster ovary (CHO) cells, allowing successful virus infection (74). There are no reports yet on the identification of receptors for the HPEV types lacking the RGD motif (HPEV3, HPEV7, and HPEV8) (19,39,51).Although the crystal structures of several picornaviruses have been determined (3,26,34,35,44,57,59,65,68,72) and the receptor interactions have been studied in detail by X-ray crystallography, electron cryo-microscopy (cryo-EM), and threedimensional (3D) image reconstruction (6,9,23,31,32,47,83), there is no structural information available for the parechoviruses or parechovirus-receptor complexes. Here, we compare the binding of ␣ V ␤ 3 and ␣ V ␤ 6 to HPEV1 in vitro by biochemical assays and determine the structures of HPEV1 and the corresponding HPEV1-integrin complexes.…”

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Interaction of α _V β ₃ and α _V β ₆ Integrins with Human Parechovirus 1

Seitsonen

Susi

Heikkilä

et al. 2010

J Virol

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Human parechovirus (HPEV) infections are very common in early childhood and can be severe in neonates. It has been shown that integrins are important for cellular infectivity of HPEV1 through experiments using peptide blocking assays and function-blocking antibodies to ␣ V integrins. The interaction of HPEV1 with ␣ V integrins is presumably mediated by a C-terminal RGD motif in the capsid protein VP1. We characterized the binding of integrins ␣ V ␤ 3 and ␣ V ␤ 6 to HPEV1 by biochemical and structural studies. We showed that although HPEV1 bound efficiently to immobilized integrins, ␣ V ␤ 6 bound more efficiently than ␣ V ␤ 3 to immobilized HPEV1. Moreover, soluble ␣ V ␤ 6, but not ␣ V ␤ 3, blocked HPEV1 cellular infectivity, indicating that it is a high-affinity receptor for HPEV1. We also showed that HPEV1 binding to integrins in vitro could be partially blocked by RGD peptides. Using electron cryo-microscopy and image reconstruction, we showed that HPEV1 has the typical T‫1؍‬ (pseudo T‫)3؍‬ organization of a picornavirus. Complexes of HPEV1 and integrins indicated that both integrin footprints reside between the 5-fold and 3-fold symmetry axes. This result does not match the RGD position predicted from the coxsackievirus A9 X-ray structure but is consistent with the predicted location of this motif in the shorter C terminus found in HPEV1. This first structural characterization of a parechovirus indicates that the differences in receptor binding are due to the amino acid differences in the integrins rather than to significantly different viral footprints.Picornaviruses consist of a positive-sense, single-stranded infectious RNA genome of approximately 7.3 kb enclosed in a capsid composed of 60 copies of each of the three or four capsid proteins (VP1 to VP4). Human parechovirus 1 (HPEV1) is a member of the Parechovirus genus of the Picornaviridae family (38, 70). There are currently eight completely sequenced human parechovirus types and 14 described types (4,19,24,30,38,39,51,58,78). In addition, the Parechovirus genus currently has four Ljungan virus members that infect rodents. HPEV1 exhibits several distinct molecular characteristics compared to other picornaviruses (38, 71). These include the lack of the maturation cleavage of the capsid proteins VP0 to VP4 (Nterminal) and VP2 (C-terminal), existence of an approximately 30-amino-acid-long extension to the N terminus of VP3, a unique nonstructural protein 2A, and a 5Ј untranslated region that is more closely related to picornaviruses infecting animals than those infecting humans.HPEV infections are common during the first years of life and are often mild or asymptomatic (20,28,42,73,80). Recently, a number of new types have been identified, and their prevalence in stool samples, for example, highlights their clinical importance. Normally, they cause gastroenteritis and respiratory infections, but severe illnesses, such as infections of the central nervous system, generalized infections of neonates, and myocarditis, have also been associated with HPEV infect...

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“…The genus Enterovirus contains Ͼ250 recognized types that can infect humans, including poliovirus (PV), echovirus (E), coxsackie A virus (CV-A), coxsackie B virus (CV-B), and rhinovirus (RV). The genus Parechovirus consists of two species, Ljungan virus and Human parechovirus (HPeV), which at present contains 16 recognized genotypes (1)(2)(3)(4)(5)(6)(7)(8). Compared to EV genotypes, which circulate simultaneously, only a few different HPeV genotypes circulate in the human population: HPeV1, -3, and -4 are the most dominant; HPeV5 and -6 are found circulating at a lower frequency; and the most recently discovered types, HPeV7 to -16, are hardly found circulating in (Western) populations.…”

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Human Memory B Cells Producing Potent Cross-Neutralizing Antibodies against Human Parechovirus: Implications for Prevalence, Treatment, and Diagnosis

Westerhuis

Benschop

Koen

et al. 2015

J Virol

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The family Picornaviridae is a large and diverse group of positive-sense RNA viruses, including human enteroviruses (EVs) and human parechoviruses (HPeVs). The human immune response against EVs and HPeVs is thought to be mainly humoral, and an insufficient neutralizing antibody (Ab) response during infection is a risk factor and can ultimately be life threatening. The accessibility of different antigenic sites and observed cross-reactivity make HPeVs a good target for development of therapeutic human monoclonal antibodies (MAbs). In this study, we generated two different human MAbs specific for HPeV by screening culture supernatants of Ab-producing human B cell cultures for direct neutralization of HPeV1. Both MAbs showed HPeV1-specific neutralization as well as neutralization of HPeV2. One antibody, AM18, cross-neutralized HPeV4, -5, and -6 and coxsackievirus A9 (CV-A9). VP1 capsid protein-specific assays confirmed that AM18 bound VP1 of HPeV1, -2, and -4 with high affinity (11.5 pM). In contrast, the HPeV1-specific MAb AM28, which neutralized HPeV1 even more efficiently than did AM18, showed no cross-reactivity with HPeV3 to -6 or other EVs and did not bind any of the capsid proteins, suggesting that AM28 is specific for a conformation-dependent, nonlinear epitope on the virus. The discovery of MAbs that are cross-reactive between HPeVs may help development of HPeV treatment options with antibodies and vaccine design based on epitopes recognized by these antibodies. IMPORTANCEHPeV infections are widespread among young children and adults, causing a broad range of disease. Infections can be severe and life threatening, while no antiviral treatment is available. Given that the absence of neutralizing Abs is a risk factor for severe disease in infants, treatment of picornavirus infections with MAbs would be a therapeutic option. To study antibody neutralization of HPeV in more detail, we generated two different HPeV1-specific human MAbs. Both MAbs show HPeV1-specific neutralization and cross-neutralized HPeV2. One MAb also cross-neutralized other HPeVs. Surprisingly, this MAb also neutralized CV-A9. These MAbs provide a unique tool for further research and for the diagnosis (antigen detection) and possible treatment of HPeV infections. T he family Picornaviridae is a large and diverse group of positive-sense RNA viruses, which consists of several important human and animal pathogens. This family contains 26 genera, including the Enterovirus and Parechovirus genera. The genus Enterovirus contains Ͼ250 recognized types that can infect humans, including poliovirus (PV), echovirus (E), coxsackie A virus (CV-A), coxsackie B virus (CV-B), and rhinovirus (RV). The genus Parechovirus consists of two species, Ljungan virus and Human parechovirus (HPeV), which at present contains 16 recognized genotypes (1-8). Compared to EV genotypes, which circulate simultaneously, only a few different HPeV genotypes circulate in the human population: HPeV1, -3, and -4 are the most dominant; HPeV5 and -6 are found circulating at ...

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Novel Human Parechovirus from Brazil

Abstract: Human parechoviruses (HPeVs) were detected by reverse transcription-PCR in 16.1% of 335 stool samples from children <6 years of age with enteritis in Salvador, Brazil. Whole genome sequencing of 1 sample showed a novel HPeV that has been designated as HPeV8.

Cited by 103 publications

References 14 publications

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

Interaction of α _V β ₃ and α _V β ₆ Integrins with Human Parechovirus 1

Human Memory B Cells Producing Potent Cross-Neutralizing Antibodies against Human Parechovirus: Implications for Prevalence, Treatment, and Diagnosis

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Novel Human Parechovirus from Brazil

Abstract: Human parechoviruses (HPeVs) were detected by reverse transcription-PCR in 16.1% of 335 stool samples from children <6 years of age with enteritis in Salvador, Brazil. Whole genome sequencing of 1 sample showed a novel HPeV that has been designated as HPeV8.

Cited by 103 publications

References 14 publications

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

Diversity of Human Parechoviruses Isolated from Stool Samples Collected from Thai Children with Acute Gastroenteritis

Interaction of α V β 3 and α V β 6 Integrins with Human Parechovirus 1

Human Memory B Cells Producing Potent Cross-Neutralizing Antibodies against Human Parechovirus: Implications for Prevalence, Treatment, and Diagnosis

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Interaction of α _V β ₃ and α _V β ₆ Integrins with Human Parechovirus 1