Tale of a tegument transactivator: the past, present and future of human CMV pp71

Herpesviruses assemble large virions capable of delivering to a newly infected cell not only the viral genome, but also viral proteins packaged within the tegument layer between the DNA-containing capsid and the lipid envelope. In this review, we describe the tegument transactivator of the β-herpesvirus human CMV, the pp71 protein. We present the known mechanistic features through which it activates viral gene expression during a lytic infection but fails to do so when the virus establishes latency, and describe how pp71 stimulates the cell cycle and may help infected cells avoid detection by the adaptive immune system. A historical overview of pp71 is extended with current perceptions of its roles during human CMV infections and suggestions for future avenues of experimentation.