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

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Deming_2021_Unlocking_the_role_of_Animals_491.pdf (1.892Mb)
Date
13/02/2021
Author
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.
Funder
NERC
Grant ID
NE/R015007/1
Keywords
California sea lion
Cancer
Urogenital carcinoma
Herpesvirus
Oncogenic virus
RNA in situ hybridization
Basescope®
QH301 Biology
QL Zoology
QR355 Virology
NDAS
SDG 3 - Good Health and Well-being
SDG 14 - Life Below Water
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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 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 (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.
Citation
Deming , A C , Wellehan , J F X , Colegrove , K M , Hall , A , Luff , J , Lowenstine , L , Duignan , P , Cortés-Hinojosa , G & Gulland , F M D 2021 , ' Unlocking the role of a genital herpesvirus, otarine herpesvirus 1, in California sea lion cervical cancer ' , Animals , vol. 11 , no. 2 , 491 . https://doi.org/10.3390/ani11020491
Publication
Animals
Status
Peer reviewed
DOI
https://doi.org/10.3390/ani11020491
ISSN
2076-2615
Type
Journal article
Rights
Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Description
This research was funded by the Geoffrey Hughes Research Fellowship and The Marine Mammal Center.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21462

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