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

This research was funded by the Geoffrey Hughes Research Fellowship and The Marine Mammal Center.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.Publisher PDFPeer reviewe

Persistent contaminants and herpesvirus OtHV1 are positively associated with cancer in wild California Sea Lions (Zalophus californianus)

This work was funded by the Geoffrey Hughes Fellowship, the National Institutes of Health (Fogarty International Center) and National Science Foundation joint program for the Ecology of Infectious Disease, the National Marine Fisheries Service Marine Mammal Heath and Stranding Program, and the Natural Environment Research Council grant number NE/R015007/.The prevalence of cancer in wild California sea lions (Zalophus californianus) is one of the highest amongst mammals, with 18–23% of adult animals examined post-mortem over the past 40 years having urogenital carcinoma. To date, organochlorines, genotype and infection with Otarine herpesvirus-1 (OtHV-1) have been identified in separate studies using distinct animals as associated with this carcinoma. Multi-year studies using large sample sizes to investigate the relative importance of multiple factors on marine mammal health are rare due to logistical and ethical challenges. The objective of this study was to use a case control approach with samples from 394 animals collected over 20 years in a multifactorial analysis to explore the relative importance of distinct factors identified to date as associated with sea lion cancer in the likelihood of sea lion carcinoma. Stepwise regression indicated that the best model to explain carcinoma occurrence included herpesvirus status, contaminant exposure, and blubber depth, but not genotype at a single microsatellite locus, PV11. The odds of carcinoma was 43.57 times higher in sea lions infected with OtHV-1 (95% CI 14.61, 129.96, p <0.001), and 1.48 times higher for every unit increase in the loge[contaminant concentrations], ng g–1 (an approximate tripling of concentration), in their blubber (95% CI 1.11, 1.97, p <0.007), after controlling for the effect of blubber depth. These findings demonstrate the importance of contaminant exposure combined with OtHV1 infection, in the potential for cancer occurrence in wild sea lions.Publisher PDFPeer reviewe

Echolocating whales and bats express the motor protein prestin in the inner ear: a potential marker for hearing loss

Prestin is an integral membrane motor protein located in outer hair cells of the mammalian cochlea. It is responsible for electromotility and required for cochlear amplification. Although prestin works in a cycle-by-cycle mode up to frequencies of at least 79 kHz, it is not known whether or not prestin is required for the extreme high frequencies used by echolocating species. Cetaceans are known to possess a prestin coding gene. However, the expression and distribution pattern of the protein in the cetacean cochlea has not been determined, and the contribution of prestin to echolocation has not yet been resolved. Here we report the expression of the protein prestin in five species of echolocating whales and two species of echolocating bats. Positive labelling in the basolateral membrane of outer hair cells, using three anti-prestin antibodies, was found all along the cochlear spiral in echolocating species. These findings provide morphological evidence that prestin can have a role in cochlear amplification in the basolateral membrane up to 120-180 kHz. In addition, labelling of the cochlea with a combination of anti-prestin, anti-neurofilament, anti-myosin VI and/or phalloidin and DAPI will be useful for detecting potential recent cases of noise-induced hearing loss in stranded cetaceans. This study improves our understanding of the mechanisms involved in sound transduction in echolocating mammals, as well as describing an optimized methodology for detecting cases of hearing loss in stranded marine mammals

Modeling population effects of the Deepwater Horizon oil spill on a long-lived species

This research was enabled partly by a grant from The Gulf of Mexico Research Initiative (GOMRI).The 2010 Deepwater Horizon (DWH) oil spill exposed common bottlenose dolphins (Tursiops truncatus) in Barataria Bay, Louisiana to heavy oiling that caused increased mortality and chronic disease and impaired reproduction in surviving dolphins. We conducted photographic surveys and veterinary assessments in the decade following the spill. We assigned a prognostic score (good, fair, guarded, poor, or grave) for each dolphin to provide a single integrated indicator of overall health, and we examined temporal trends in prognostic scores. We used expert elicitation to quantify the implications of trends for the proportion of the dolphins that would recover within their lifetime. We integrated expert elicitation, along with other new information, in a population dynamics model to predict the effects of observed health trends on demography. We compared the resulting population trajectory with that predicted under baseline (no spill) conditions. Disease conditions persisted and have recently worsened in dolphins that were presumably exposed to DWH oil: 78% of those assessed in 2018 had a guarded, poor, or grave prognosis. Dolphins born after the spill were in better health. We estimated that the population declined by 45% (95% CI 14–74) relative to baseline and will take 35 years (95% CI 18–67) to recover to 95% of baseline numbers. The sum of annual differences between baseline and injured population sizes (i.e., the lost cetacean years) was 30,993 (95% CI 6607–94,148). The population is currently at a minimum point in its recovery trajectory and is vulnerable to emerging threats, including planned ecosystem restoration efforts that are likely to be detrimental to the dolphins’ survival. Our modeling framework demonstrates an approach for integrating different sources and types of data, highlights the utility of expert elicitation for indeterminable input parameters, and emphasizes the importance of considering and monitoring long-term health of long-lived species subject to environmental disasters. Article impact statement: Oil spills can have long-term consequences for the health of long-lived species; thus, effective restoration and monitoring are needed.Publisher PDFPeer reviewe

A review of the toxicology of oil in vertebrates : what we have learned following the Deepwater Horizon oil spill

This research was made possible by a grant from The Gulf of Mexico Research Initiative. This publication is UMCES contribution No. 6045 and Ref. No. [UMCES] CBL 2022-008. This is National Marine Mammal Foundation Contribution #314 to peer-reviewed scientific literature.In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.Publisher PDFPeer reviewe

Phocine distemper Virus: Current knowledge and future directions

Phocine distemper virus (PDV) was first recognized in 1988 following a massive epidemic in harbor and grey seals in north-western Europe. Since then, the epidemiology of infection in North Atlantic and Arctic pinnipeds has been investigated. In the western North Atlantic endemic infection in harp and grey seals predates the European epidemic, with relatively small, localized mortality events occurring primarily in harbor seals. By contrast, PDV seems not to have become established in European harbor seals following the 1988 epidemic and a second event of similar magnitude and extent occurred in 2002. PDV is a distinct species within the Morbillivirus genus with minor sequence variation between outbreaks over time. There is now mounting evidence of PDV-like viruses in the North Pacific/Western Arctic with serological and molecular evidence of infection in pinnipeds and sea otters. However, despite the absence of associated mortality in the region, there is concern that the virus may infect the large Pacific harbor seal and northern elephant seal populations or the endangered Hawaiian monk seals. Here, we review the current state of knowledge on PDV with particular focus on developments in diagnostics, pathogenesis, immune response, vaccine development, phylogenetics and modeling over the past 20 years