Viral and host network analysis of the human cytomegalovirus transcriptome in latency

HCMV genes <i>UL135</i> and <i>UL138</i> play opposing roles regulating latency and reactivation in CD34⁺ human progenitor cells (HPCs). Using the THP-1 cell line model for latency and reactivation, we designed an RNA sequencing study to compare the transcriptional profile of HCMV infection in the presence and absence of these genes. The loss of <i>UL138</i> results in elevated levels of viral gene expression and increased differentiation of cell populations that support HCMV gene expression and genome synthesis. The loss of <i>UL135</i> results in diminished viral gene expression during an initial burst that occurs as latency is established and no expression of eleven viral genes from the UL<i>b</i>' region even following stimulation for differentiation and reactivation. Transcriptional network analysis revealed host transcription factors with potential to regulate the UL<i>b</i>' genes in coordination with pUL135. These results reveal roles for <i>UL135</i> and <i>UL138</i> in regulation of viral gene expression and potentially hematopoietic differentiation.