Recently, HCMV infection has been shown to be associated with cancer development 6. Human cytomegalovirus (HCMV), the prototypical member of the Betaherpesvirinae subfamily, is the leading pathogenic cause of birth abnormalities, and morbidity and mortality in immunocompromised individuals, such as patients with AIDS and transplant recipients 1, 2, 3, 4, 5. These findings unravel the mechanism by which the portal interacts with the scaffold to nucleate capsid assembly and further our understanding of scaffold expulsion and DNA incorporation. The portal also undergoes significant changes both positionally and conformationally as it accompanies DNA packaging. We further show that 12 loop-helix-loop fragments-presumably from the scaffold domain-insert into the hydrophobic pocket of the portal crown domain. We show that scaffolds bind to the hydrophobic cavities formed by the dimerization and Johnson-fold domains of the major capsid proteins. Here we present high-resolution structures of the A- and B-capsids and in-situ portals of human cytomegalovirus. The portal-scaffold interaction and the conformational changes that occur to the portal during the different stages of capsid formation have yet to be elucidated structurally. During capsid maturation, two events occur: scaffold expulsion and DNA incorporation. The portal-scaffold complex is believed to nucleate the assembly of herpesvirus procapsids.

Scaffold protein loop domain