Interaction of Human Cytomegalovirus PUL52 with Major Components of the Viral DNA Encapsidation Network Underlines Its Essential Role in Genome Cleavage-packaging

Importance: Human cytomegalovirus (HCMV) can evoke severe disease in immunocompromised patients and, moreover, is the most frequent viral cause of malformations in newborns. The virus-specific process of genome cleavage and packaging into capsids has emerged as an Achilles heel in the HCMV life cycle, which can be targeted by novel antiviral drugs, yet the mechanism of viral DNA encapsidation is only partially understood. Here, we report that the essential viral cleavage-packaging protein pUL52 interacts with several HCMV proteins known to be crucial for genome packaging, with the most prominent ones being the terminase complex and the portal protein. These data provide insight into the role of pUL52 during HCMV infection and may lay the basis for the development of additional antiviral substances tackling viral DNA packaging.