The herpes simplex virus type 2 (HSV-2) UL21 protein is conserved between all members of the Alphaherpesvirinae subfamily. Although UL21 is essential for virus propagation in HSV-2, its function in viral replication is poorly understood. Cells infected with HSV-2 strains lacking UL21 exhibit an approximate two-hour delay in viral gene expression that cannot be explained by a defect in virus entry or capsid engagement with, or movement along, microtubules. However, we noted a defect in the ability of UL21 knockout (KO21) capsids to associate with the nucleus after infection. We found that the delay in viral gene expression was not directly due to the absence of UL21 insofar as cells stably expressing UL21 could not complement the delay in gene expression. We suggest that the KO21 delay in gene expression is due to alterations in virion composition and that in the absence of UL21, a key virion component required for the timely delivery of capsids to the nucleus fails to be packaged into virions. Interestingly, at late times after infection, levels of viral proteins in KO21 infected cells reach wild-type levels, indicating that a secondary function is responsible for the essential nature of UL21. We found that at late times post-infection KO21 infected cells accumulated capsids in the nucleus but these fail to reach the cytoplasm and mature into infectious virions. Thus, we hypothesize that the essential function of UL21 is to facilitate capsid trafficking from the nucleus to the cytoplasm. Moreover, the viral glycoproteins gD and gC were retained in the endoplasmic reticulum, and were under-glycosylated in KO21 infected cells. It is therefore possible that the absence of UL21 prevents the targeting of glycoproteins to the inner nuclear membrane, preventing the formation or function of the nuclear egress complex. / Thesis (Master, Microbiology & Immunology) -- Queen's University, 2013-09-10 16:20:32.162