In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk

Selariu, Anca; Powers, Jenny G.; Nalls, Amy V.; Brandhuber, Monica; Mayfield, Amber; Fullaway, Stephenie; Wyckoff, Christy; Goldmann, Wilfred; Zabel, Mark; Wild, Margaret A.; Hoover, Edward A.; Mathiason, Candace K.

doi:10.1099/jgv.0.000281

Cited by 45 publications

(57 citation statements)

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“…Because the offspring were born to and raised by their infected mothers, we were unable to parse the point source of infectivity, i.e., whether infection originated from contact with maternal prions during parturition or shortly thereafter or via in utero exposure. We addressed this question by revealing amplification-competent prions in in utero-harvested fetal tissues from CWD-infected muntjac dams regardless of disease or gestational stage (1) and in reproductive and fetal tissues harvested from free-range cervid dams naturally exposed to CWD but not presenting clinical signs of disease (preclinical dams) (2). What remained unanswered was whether the prions detected in in utero-harvested tissues were infectious.…”

Section: Discussionmentioning

confidence: 99%

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Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Nalls

McNulty

Hoover

et al. 2017

J Virol

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Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e., Zika virus, brucella, cytomegalovirus, and toxoplasma). While less studied, pregnancyrelated transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother to offspring, resulting in the development of clinical TSE disease in offspring born to muntjac dams infected with chronic wasting disease (CWD) (1). We further demonstrated protein misfolding cyclic amplification (PMCA)-competent prions within the female reproductive tract and in fetal tissues harvested from CWD experimentally and naturally exposed cervids (1, 2). To assess whether the PMCA-competent prions residing at the maternal-fetal interface were infectious and to determine if the real-time quaking-induced conversion (RT-QuIC) methodology may enhance our ability to detect amyloid fibrils within the pregnancy microenvironment, we employed a mouse bioassay and RT-QuIC. In this study, we have demonstrated RT-QuIC seeding activity in uterus, placentome, ovary, and amniotic fluid but not in allantoic fluids harvested from CWD-infected Reeves' muntjac dams showing clinical signs of infection (clinically CWD-infected) and in some placentomes from pre-clinically CWD-infected dams. Prion infectivity was confirmed within the uterus, amniotic fluid, and the placentome, the semipermeable interface that sustains the developing fetus, of CWD-infected dams. This is the first report of prion infectivity within the cervid pregnancy microenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal grooming, or encounters with contaminated environments.IMPORTANCE The facile dissemination of chronic wasting disease within captive and free-range cervid populations has led to questions regarding the transmission dynamics of this disease. Direct contact with infected animals and indirect contact with infectious prions in bodily fluids and contaminated environments are suspected to explain the majority of this transmission. A third mode of transmission, from mother to offspring, may be underappreciated. The presence of pregnancyrelated prion infectivity within the uterus, amniotic fluid, and the placental structure reveals that the developing fetus is exposed to a source of prions long before exposure to the infectious agent during and after the birthing process or via contact with contaminated environments. These findings have impact on our current concept of CWD disease transmission.KEYWORDS CWD, maternal, pregnancy, prions T ransmissible spongiform encephalopathies (TSEs), or prion diseases, are proteinaceous infectious neurodegenerative diseases affecting animals, including humans (3, 4). The disease is caused by the accumulation of an aberrant misfolded form

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Section: Discussionmentioning

confidence: 99%

“…We were not able to detect PrP RES deposition in placentomes by Western blot analysis or immunohistochemistry (data not shown), similar to other maternal reproductive tissues, yet we were able to demonstrate PMCA seeding activity in tissues at this intimate interface between mother and fetus (1,2). Thus, RT-QuIC and bioassay studies were initiated.…”

mentioning

confidence: 99%

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Nalls

McNulty

Hoover

et al. 2017

J Virol

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“…Experiments and observations demonstrate that CWD prion transmission can occur vertically (e.g. mother to offspring) (Selariu et al ., ) or horizontally (e.g. direct animal contact, environmental infection) (Mathiason et al ., ; Denkers et al ., ; Zabel & Ortega, ) (Fig.…”

Section: Chronic Wasting Disease Biology Epidemiology and Transmissionmentioning

confidence: 99%

The ecology of chronic wasting disease in wildlife

et al. 2019

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Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.

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“…CWD was first detected in cervids in the late 1960s in Colorado [2,3] and has since spread to an increasing number of other US states and Canadian provinces [4,5]. The disease is transmitted horizontally by contact with pathogenic prions shed in bodily fluids [6,7] and vertically from mother to offspring [8,9]. Once shed, prions have been shown to persist in the environment, potentially remaining infectious and furthering disease spread long after affected deer have dispersed [10–12].…”

Section: Introductionmentioning

confidence: 99%

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

Brandt

Green

Ishida

et al. 2018

Prion

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Managing and controlling the spread of diseases in wild animal populations is challenging, especially for social and mobile species. Effective management benefits from information about disease susceptibility, allowing limited resources to be focused on areas or populations with a higher risk of infection. Chronic wasting disease (CWD), a transmissible spongiform encephalopathy that affects cervids, was detected in Colorado in the late 1960s. CWD was detected in Illinois and Wisconsin in 2002 and has since spread through many counties. Specific nucleotide variations in the prion protein gene (PRNP) sequence have been associated with reduced susceptibility to CWD in white-tailed deer. Though genetic resistance is incomplete, the frequency of deer possessing these mutations in a population is an important factor in disease spread (i.e. herd immunity). In this study we sequenced 625 bp of the PRNP gene from a sampling of 2433 deer from Illinois and Wisconsin. In north-central Illinois where CWD was first detected, counties had a low frequency of protective haplotypes (frequency <0.20); whereas in northwestern Illinois counties, where CWD cases have only more recently been detected, the frequency of protective haplotypes (frequency >0.30) was much higher (p < 0.05). Protective haplotype frequencies varied significantly among infected and uninfected geographic areas. The frequency of protective PRNP haplotypes may contribute to population level susceptibility and may shape the way CWD has spread through Illinois. Analysis of PRNP haplotype distribution could be a useful tool to assess CWD risk and allocate resources to contain and reduce the spread of infection.

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In utero transmission and tissue distribution of chronic wasting disease-associated prions in free-ranging Rocky Mountain elk

Cited by 45 publications

References 46 publications

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

The ecology of chronic wasting disease in wildlife

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

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