Functional Conservations of the Alkaline Nuclease of Herpes Simplex Type 1 and Human Cytomegalovirus

Abstract

The herpes simplex virus type 1 UL12 gene product, alkaline nuclease (AN), appears to be involved in viral DNA processing and capsid egress from the nucleus (Shao, L., Rapp, L. M., and Weller, S. K.,Virology196, 146–162, 1993). Although the HSV-1 AN is not absolutely essential for viral replication in tissue culture, conservation of the AN gene in all herpesviruses suggests an important role in the life cycle of herpesviruses. The counterpart of HSV-1 AN for human cytomegalovirus (HCMV) is the UL98 gene product. To examine whether the HCMV AN could substitute for HSV-1 AN, we performedtrans-complementation experiments using a HSV-1 amplicon plasmid carrying the HCMV UL98 gene. Our results indicate (i) HCMV AN can complement the growth of the HSV-1 AN deletion mutantUL12lacZvirus intrans;(ii) a new recombinant virus,UL12laZcUL98/99,appears to be generated by the integration of the HCMV UL98 gene into the HSV-1UL12lacZviral genome; (iii) in contrast to its parental HSV-1UL12lacZvirus, capsids formed inUL12lacZUL98/99-infected Vero cells were able to transport from the nucleus to the cytoplasm and mature into infectious viruses. Our results demonstrate a functional conservation of AN between HSV-1 and HCMV.