Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and therapy development

Abstract

Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is associated with mild disease, HPeV3 is the cause of neonatal sepsis and meningitis. To test whether in vitro replication kinetics of HPeV1 and HPeV3 could be related to pathogenicity, HPeV1 and HPeV3 strains isolated from patients were cultured on cell lines of gastrointestinal, respiratory and neural origin, and replication kinetics were measured by real-time PCR. No relationship was found between clinical symptoms and in vitro replication of the HPeV1 strains. In contrast, the HPeV3 strains showed faster replication in neural cells and there was a relationship between higher in vitro replication kinetics and neuropathogenicity in the patient. Furthermore, HPeV1 could be neutralized efficiently by its specific antibody and by intravenous immunoglobulins (IVIG), while most HPeV3 strains could not be neutralized. In IVIG, very low neutralizing antibody (nAb) titres against HPeV3 were found. Additionally, very low nAb titres were observed in sera of two HPeV3-infected donors, while high nAb titres against HPeV1 could be detected. Our data suggest that the mild clinical course of HPeV1 infection is primarily influenced by strong nAb responses, while HPeV3 might be difficult to neutralize in vivo and therefore the course of infection will mainly be determined by in vivo cell tropism.

Virus Antibody Survey in Different European Populations Indicates Risk Association Between Coxsackievirus B1 and Type 1 Diabetes

“…This is seen clearly in patients with antibody deficiencies who can develop severe and chronic EV infections. This scenario has been proposed for human parechoviruses, which are close relatives of EVs (25).…”

Parechovirus Encephalitis and Neurodevelopmental Outcomes

“…48,49 Additionally, in vitro studies show that HPeV3 has specific neuronal tropism. 50 This may explain how HPeV3 CNS infection can result in significant tissue damage, in the absence of CSF pleocytosis, and relatively low viral loads seen in CSF. 14,25 There are few cases of HPEV3 CNS infection with published histopathology to contribute to our understanding.…”

Parechovirus como agente etiológico de meningitis y/o sepsis viral en lactantes

“…Westerhuis y cols. 40 , estudiaron cepas de HPeV 1 y HPeV 3 en cultivos de células intestinales, respiratorias y neuronas, aplicando RPC en tiempo real con el objetivo de verificar si la cinética de replicación viral in vitro de HPeV 1 y HPeV 3 se relacionaba con la patogenicidad. No se encontró relación al comparar los síntomas clínicos de HPeV 1 y la replicación in vitro de las cepas HPeV 1.…”

“…Por el contrario, las cepas HPeV 3 mostraron una replicación más rápida en las células neuronales y hubo relación entre la mayor cinética de replicación in vitro y la neuro-patogenicidad en el paciente. Además HPeV 1 pudo ser neutralizado por su anticuerpo específico y por inmunoglobulina endovenosa, mientras que la mayoría de las cepas HPeV 3 no pudieron ser neutralizadas 19,40 . Estos hallazgos podrían apoyar la gravedad de HPeV 3.…”