Deming Alissa C, Wellehan James F X, Colegrove Kathleen M, Hall Ailsa, Luff Jennifer, Lowenstine Linda, Duignan Pádraig, Cortés-Hinojosa Galaxia, Gulland Frances M D
The Pacific Mammal Center, Laguna Beach, CA 92651, USA.
Aquatic Animal Health and Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.
Animals (Basel). 2021 Feb 13;11(2):491. doi: 10.3390/ani11020491.
Urogenital carcinoma in California sea lions () is the most common cancer of marine mammals. Primary tumors occur in the cervix, vagina, penis, or prepuce and aggressively metastasize resulting in death. This cancer has been strongly associated with a sexually transmitted herpesvirus, otarine herpesvirus 1 (OtHV1), but the virus has been detected in genital tracts of sea lions without cancer and a causative link has not been established. To determine if OtHV1 has a role in causing urogenital carcinoma we sequenced the viral genome, quantified viral load from cervical tissue from sea lions with ( = 95) and without ( = 163) urogenital carcinoma, and measured viral mRNA expression using in situ mRNA hybridization (Basescope) to quantify and identify the location of OtHV1 mRNA expression. Of the 95 sea lions diagnosed with urogenital carcinoma, 100% were qPCR positive for OtHV1, and 36% of the sea lions with a normal cervix were positive for the virus. The non-cancer OtHV1 positive cases had significantly lower viral loads in their cervix compared to the cervices from sea lions with urogenital carcinoma. The OtHV1 genome had several genes similar to the known oncogenes, and RNA in situ hybridization demonstrated high OtHV1 mRNA expression within the carcinoma lesions but not in normal cervical epithelium. The high viral loads, high mRNA expression of OtHV1 in the cervical tumors, and the presence of suspected OtHV1 oncogenes support the hypothesis that OtHV1 plays a significant role in the development of sea lion urogenital carcinoma.
加利福尼亚海狮的泌尿生殖系统癌是海洋哺乳动物中最常见的癌症。原发性肿瘤发生在子宫颈、阴道、阴茎或包皮，并具有侵袭性转移，最终导致死亡。这种癌症与一种性传播的疱疹病毒——海狗疱疹病毒1（OtHV1）密切相关，但在未患癌症的海狮生殖道中也检测到了该病毒，且尚未确定其因果关系。为了确定OtHV1是否在泌尿生殖系统癌的发生中起作用，我们对病毒基因组进行了测序，对患有（n = 95）和未患有（n = 163）泌尿生殖系统癌的海狮宫颈组织中的病毒载量进行了定量，并使用原位mRNA杂交（Basescope）测量病毒mRNA表达，以定量和确定OtHV1 mRNA表达的位置。在95只被诊断患有泌尿生殖系统癌的海狮中，100%的OtHV1 qPCR检测呈阳性，而宫颈正常的海狮中有36%的病毒检测呈阳性。与患有泌尿生殖系统癌的海狮宫颈相比，未患癌症的OtHV1阳性病例宫颈中的病毒载量显著更低。OtHV1基因组有几个与已知癌基因相似的基因，RNA原位杂交显示癌灶内OtHV1 mRNA高表达，而正常宫颈上皮中则无。高病毒载量、宫颈肿瘤中OtHV1的高mRNA表达以及疑似OtHV1癌基因的存在支持了OtHV1在海狮泌尿生殖系统癌发生中起重要作用的假说。
