Human parechovirus seroprevalence in Finland and the Netherlands

Westerhuis, Brenda M.; Kolehmainen, Pekka; Benschop, Kimberley; Nurminen, Noora; Koen, Gerrit; Koskiniemi, Marjaleena; Simell, Olli; Knip, Mikael; Hyöty, Heikki; Wolthers, Katja C.; Tauriainen, Sisko

doi:10.1016/j.jcv.2013.06.036

Cited by 54 publications

(57 citation statements)

References 33 publications

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“…We showed that both MAbs discovered by directly screening for HPeV1 neutralization also neutralized HPeV2, indicating that HPeV1 and -2 share similar neutralizing epitopes. This cross-reactivity with HPeV2, although observed in only two donors, may explain why a high seroprevalence of antibodies against HPeV2 is found in the Netherlands and Finland (86 to 99%) (26), while HPeV2 infections are hardly detected (35,40,41). In addition, the HPeV1-specific MAb AM18 also cross-neutralized HPeV4, -5, and -6 but not HPeV3.…”

Section: Discussionmentioning

confidence: 92%

“…These differences in pathogenesis and cytopathogenicity between different HPeV types could be related to differences in receptor usage (as has been shown for HIV-1 [54]) and differences in the timing and quality of the developing antibody response. The antibody response against HPeV3 may be weak, since detection of neutralizing Abs against HPeV3 in serum was difficult (26,29), leaving a challenge to find a protective MAb against HPeV3 in the future.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, several studies showed that cross-neutralization may exist for HPeVs. In Finland and the Netherlands, the seroprevalences of neutralizing Abs were 92% for HPeV1 and 86% for HPeV2 in sera from adults (24)(25)(26). There is no evidence that HPeV2 circulates in these countries, suggesting that cross-neutralization may exist for HPeV1 and -2.…”

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confidence: 97%

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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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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…A study of sera from different populations in Finland and the Netherlands only revealed neutralizing responses to HPeV-3 in about 10 % of the samples and very low titres of neutralizing antibodies post-infection [175]. By contrast, researchers in Japan detected neutralizing responses to HPeV-3 in 67 % of individuals between 7 months and 40 years old [94], and reported high titres of neutralizing antibodies after 3 months post-infection in all studied individuals [176].…”

Section: Neutralization Of Hpev-3mentioning

confidence: 95%

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

Anastasina

Domanska

Palm

et al. 2017

Journal of General Virology

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Picornaviruses are the most commonly encountered infectious agents in mankind. They typically cause mild infections of the gastrointestinal or respiratory tract, but sometimes also invade the central nervous system. There, they can cause severe diseases with long-term sequelae and even be lethal. The most infamous picornavirus is poliovirus, for which significant epidemics of poliomyelitis were reported from the end of the nineteenth century. A successful vaccination campaign has brought poliovirus close to eradication, but neurological diseases caused by other picornaviruses have increasingly been reported since the late 1990s. In this review we focus on enterovirus 71, coxsackievirus A16, enterovirus 68 and human parechovirus 3, which have recently drawn attention because of their links to severe neurological diseases. We discuss the clinical relevance of these viruses and the primary role of humoral immunity in controlling them, and summarize current knowledge on the neutralization of such viruses by antibodies.

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“…This almost universal infection early in life does not appear to occur with HPeV-3, with a small study from Japan showing a seroprevalence of 15% at seven to 12 months of age, 45% at two to three years of age and 85% at four to six years of age (21). A study involving adults in Finland and the Netherlands showed seroprevalence rates of >85% for HPeV-1 and HPeV-2 and 35% to 75% for HPeV-4, -5 and -6, but only approximately 10% for HPeV-3 (39). None of 59 adults tested for HIV in Milwaukee (Wisconsin, USA) had antibodies to HPeV-3 (26).…”

Section: Epidemiology and Clinical Manifestationsmentioning

confidence: 99%