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Phenotypic and genetic polymorphisms among human herpesvirus-6 isolates from North American infants
S Dewhurst1, B Chandran, K McIntyre
1Department of Microbiology and Immunology, University of Rochester Medical Center, New York 14642.
Insights
Human herpesvirus-6 (HHV-6) isolates from infants show varied replication patterns. Some infant HHV-6 isolates exhibit characteristics previously seen only in adult strains, challenging traditional classifications.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human herpesvirus-6 (HHV-6) is a common viral infection in infants, often presenting as febrile illness or roseola (exanthem subitum).
- HHV-6 isolates have been broadly classified into two groups, A and B, based on in vitro characteristics and reactivity with monoclonal antibodies.
Purpose of the Study:
- To phenotypically and genotypically characterize HHV-6 isolates from North American infants with primary infections.
- To investigate the in vitro growth patterns and antibody reactivity of these infant HHV-6 isolates in different cell types.
- To assess the validity of current HHV-6 classification systems based on observed isolate characteristics.
Main Methods:
- Phenotypic characterization of 15 HHV-6 infant isolates based on in vitro replication in T-cell lines (HSB-2) and primary human mononuclear cells.
- Assessment of viral reactivity using a panel of monoclonal antibodies.
- Genomic characterization using restriction site polymorphisms to analyze viral DNA.
Main Results:
- All 15 HHV-6 isolates replicated efficiently in primary human cord blood mononuclear cells.
- Five distinct patterns of viral replication were observed in human cell lines.
- Two infant HHV-6 isolates replicated in HSB-2 cells and reacted with A-specific monoclonal antibodies, properties previously associated with Group A viruses.
- Genomic analysis revealed these two isolates contained a mixture of both HHV-6 A and B type genomes in varying proportions.
Conclusions:
- The findings challenge the strict categorization of HHV-6 isolates into distinct Group A and Group B.
- Some HHV-6 isolates from infants exhibit mixed genomic characteristics, suggesting a more complex classification is needed.
- Segregating HHV-6 isolates into only two broad groups may be misleading and oversimplified.
Abstract:
Fifteen human herpesvirus-6 (HHV-6) isolates from North American infants with primary infection manifest as febrile or roseola (exanthem subitum) like illnesses were characterized phenotypically on the basis of their in vitro growth in continuous T-cell lines and primary human mononuclear cells and by their reactivity with monoclonal antibodies. All isolates replicated efficiently in primary human cord blood mononuclear cells, but five distinct patterns of viral replication in human cells lines were observed. Two of the HHV-6 isolates from infants were found to replicate in HSB-2 cells, a property associated with so-called group A viruses, which had previously been isolated only from adults. These same isolates also reacted with a panel of A-specific monoclonal antibodies. Genomic characterization of viral isolates using well-characterized restriction site polymorphisms indicated that these two isolates contained a mixture of both A- and B-type genomes, in different proportions. These data suggest that not all HHV-6 isolates can be categorized into one of two broad groups and that such segregation of HHV-6 isolates may in fact be misleading.