Fred L. Homa, PhD

The goal of our research is to understand an important step of virus assembly: (i) how the herpesvirus capsid is assembled, (ii) how the viral genome is packaged into the capsid, and (iii) how viral capsid interacts with and releases the viral genome into the nucleus of newly infected cells. DNA encapsidation and cleavage involves the coordinated interaction of several HSV proteins that are essential for production of infectious virions. The HSV-1 genome is translocated into the icosahedral procapsid through a donut-shaped “portal” that is present at one of the 12 vertices of the procapsid. This process is directed by the terminase complex, which consists of the HSV UL15, UL28, and UL33 proteins that function both as part of the ATP-hydrolyzing pump which drives DNA into the capsid, and a nuclease that cuts the concatemeric DNA at specific sites to yield a capsid containing the intact genome. The capsid is then stabilized by the addition of the capsid vertex specific component (CVSC), which functions to retain the packaged DNA and to signal for nuclear egress of the mature DNA-filled capsid, as well as for nuclear attachment of the incoming, infecting capsid. Understanding the herpesvirus portal structure and its interaction with the packaging machinery has been hampered due to the subtle differences between the portal-vertex and penton-vertices. However, recent advances in cryoEM have allowed portals to be localized in images of intact capsids yielding important structural information with regards to the portal and associated proteins.