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Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and
Brenda M Westerhuis1, Gerrit Koen1, Joanne G Wildenbeest2,1
1Department of Medical Microbiology, Laboratory of Clinical Virology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
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.
Insights
Human parechoviruses (HPeVs) show different disease potentials. HPeV1 causes mild illness due to strong antibody responses, while HPeV3 causes severe disease, potentially due to poor neutralization and neural cell tropism.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Human parechoviruses (HPeVs) are common picornaviruses.
- HPeV1 is linked to mild infections, whereas HPeV3 causes severe neonatal sepsis and meningitis.
Purpose of the Study:
- To investigate the relationship between in vitro replication kinetics and pathogenicity of HPeV1 and HPeV3.
- To assess the neutralization capacity of antibodies against HPeV1 and HPeV3.
Main Methods:
- Culturing HPeV1 and HPeV3 strains on gastrointestinal, respiratory, and neural cell lines.
- Measuring viral replication kinetics using real-time PCR.
- Assessing neutralization by specific antibodies and intravenous immunoglobulins (IVIG).
Main Results:
- No correlation between in vitro replication and clinical symptoms for HPeV1 strains.
- HPeV3 strains replicated faster in neural cells, correlating with neuropathogenicity.
- HPeV1 was efficiently neutralized by antibodies and IVIG, unlike most HPeV3 strains, which showed low neutralizing antibody titers.
Conclusions:
- Mild HPeV1 infections are associated with robust neutralizing antibody responses.
- HPeV3's difficulty in neutralization in vivo suggests cell tropism is a key factor in its pathogenicity.
- Differences in antibody neutralization and cell tropism explain the varying clinical outcomes of HPeV1 and HPeV3 infections.
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