Human cytomegalovirus intrahost evolution - a new avenue for understanding and controlling herpesvirus infections

•Cytomegaloviruses rapidly evolve within individual hosts.•Human cytomegalovirus (HCMV) genetic diversity rivals that of some RNA viruses.•Transmission dynamics, reinfection, and recombination can alter diversity.•Standing variation allows HCMV populations to adapt rapidly to changing environments.•Targeting HCMV diversity and evolution is a novel therapeutic strategy.

Human cytomegalovirus (HCMV) is exquisitely adapted to the human host, and much research has focused on its evolution over long timescales spanning millennia. Here, we review recent data exploring the evolution of the virus on much shorter timescales, on the order of days or months. We describe the intrahost genetic diversity of the virus isolated from humans, and how this diversity contributes to HCMV spatiotemporal evolution. We propose mechanisms to explain the high levels of intrahost diversity and discuss how this new information may shed light on HCMV infection and pathogenesis.