Viral and host gene expression patterns in human herpesvirus type-7 infection of T-cells
Human herpesvirus type 7 (HHV-7), with its high prevalence and apparently non pathogenic nature, is believed to be a virus very well adapted to humans. It is therefore useful to study the transcription patterns of the virus and the host to understand the life cycle and pathogenesis (or the lack of it) of HHV-7 infection. In order to obtain the global pattern of host and viral gene expression, we have made a DNA microarray containing probes that target all 86 predicted HHV-7 open reading frames and approximately 1000 cellular genes. This is the first description of an integrated host- pathogen microarray for HHV-7. The microarrays were used to follow the gene expression patterns over a 72-hour time course infection of a CD4+ T-cell line (Sup-Tl) by HHV-7 in vitro, which revealed an overall increase of HHV-7 transcripts over time, as well as the coordinated transcription profiles for groups of viral genes with similar functions. HHV-7 genes predicted to be immediate-early transcription factors were the first genes to be expressed, followed by genes involved in viral DNA replication, and at later stages, the genes encoding structural proteins and proteins of packaging functions were expressed. Temporal classification was assigned for 68 HHV-7 ORFs, of which a selection was confirmed by RT-PCR in the presence of metabolic inhibitors of de novo protein synthesis and viral DNA replication. Both gene expression profiling and inhibitor treatment demonstrated that the lytic gene expression of HHV-7 was temporally regulated, consistent with the classification of viral gene expression into immediate-early, early and late transcripts in other herpesviruses.