Intrinsic cellular defense mechanisms targeting human cytomegalovirus

In recent studies we and others have identified the cellular proteins PML, hDaxx, Sp100 and ATRX, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract cytomegalovirus infections by inhibiting the initiation of viral immediate-early (IE) gene expression. The antiviral function of ND10, however, is antagonized by viral regulatory proteins which either induce a proteasomal degradation of ND10 proteins or a disruption of the subnuclear structure. This review will summarize our current knowledge on the inhibition of cytomegalovirus replication by ND10 proteins. Furthermore, viral strategies to defeat this host defense mechanism are discussed.