Although HHV-6A and -6B are known to replicate preferably in human T-lymphocytes, in vitro infection of several other cell types has been described. Also, the finding that both variants use the ubiquitous molecule CD46 as a membrane receptor fully supports the possibility of a broad cellular tropism. However, productive infection, which requires complete progression through the viral replication cycle, depends on multiple cellular processes. Our studies were aimed at determining the differences in replication efficiency according to the cell type infected and at relating these differences to the sequential transcriptional events preceding DNA replication. A strong expression of immediate-early, early, and late genes was only seen in the T-lymphoblastoma lines. In the other cell lines, there was no clear correlation between the level of transcription and the final outcome of replication. Finally, we investigated the cytopathic effects of HHV-6 on different cell types of neural origin (oligodendrocytes, astrocytes, and neurons) in greater detail, and found that although all three sustained HHV-6 replication, HHV-6A was more neurovirulent than HHV-6B. This was confirmed in primary human oligodendrocyte cultures.
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