Investigations into the association between otarine herpesvirus 1 and endemic cancer in California sea lions (Zalophus californianus): Age class, tissue distribution and in vitro cultivation of the virus

Over the last 25 years, laboratories at the University of California, Davis and The Marine Mammal Center, a wildlife rehabilitation center in Sausalito, California, have collaborated to document the causes of death in stranded marine mammals along the California coast. As a result of this collaboration, a significant prevalence of neoplasia was documented in the adult California sea lions (Zalophus californianus) dying during the rehabilitation process. The most common neoplasm diagnosed was a highly aggressive urogenital carcinoma, which metastasized early and widely. Close histopathological examination of these neoplasms showed the presence of intranuclear inclusion bodies in some of the neoplastic cells. Electron microscopic examination showed these to be herpesviral inclusions as subsequent polymerase chain reaction (PCR) studies showed that this virus was related to Human Herpesvirus 8, the causative agent of Kaposi's sarcoma in humans. The purpose of this dissertation was to conduct an initial survey of the OtHV-1 distribution in the sea lion population, determine if the virus is associated with urogenital carcinomas and to cultivate OtHV-1 in vitro.; The results presented in this dissertation document a statistical association between the virus and the presence of urogenital tumors, show that the relationship between the urogenital carcinomas and the tumors in unique and document that OtHV-1 is endemic in the free ranging population of sea lions, most often detected in the genital tract of the adults. Furthermore, histological studies of the female sea lion reproductive tract demonstrate that the ovarian and uterine cycle of the female sea lion has unique features, as does the cervical anatomy. Such features could predispose the sea lions to OtHV-1 infection. Finally, OtHV-1 was cultured on primary sea lion fibroblasts. Thought proving causality between OtHV-1 and cancer development is beyond the scope of this dissertation, the results indicated that further study is warranted. Furthermore, the cultivation of the virus in vitro provides one of the initial tools needed for further mechanistic studies.