Unlocking the role of a genital herpesvirus, otarine herpesvirus 1, in california sea lion cervical cancer

Alissa C. Deming, James F.X. Wellehan, Kathleen M. Colegrove, Ailsa Hall, Jennifer Luff, Linda Lowenstine, Pádraig Duignan, Galaxia Cortés-Hinojosa, Frances M.D. Gulland

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Urogenital carcinoma in California sea lions (Zalophus californianus) is the most common cancer of marine mammals. Primary tumors occur in the cervix, vagina, penis, or prepuce and ag-gressively 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 (n = 95) and without (n = 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.

Original languageEnglish (US)
Article number491
Pages (from-to)1-17
Number of pages17
JournalAnimals
Volume11
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • Basescope®
  • California sea lion
  • Cancer
  • Herpesvirus
  • Oncogenic virus
  • RNA in situ hybridization
  • Urogenital carcinoma

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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