Our results suggest a potential mechanism by which HCMV latent infection downregulates S100A8/A9: repressive CTCF binding to the enhancer region of the S100A8/A9 genomic locus is increased during HCMV latency, likely mediated by the viral gene product US28. This evidence concerns the gene IGKV1D-22 and disease arising from reactivation of latent virus.