Susceptibilities of Nonhuman Primates to CWD | CDC EID

Volume 15, Number 9–September 2009
Research
Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
Brent Race,1 Kimberly D. Meade-White,1 Michael W. Miller, Kent D. Barbian, Richard Rubenstein, Giuseppe LaFauci, Larisa Cervenakova, Cynthia Favara, Donald Gardner, Dan Long, Michael Parnell, James Striebel, Suzette A. Priola, Anne Ward, Elizabeth S. Williams,2 Richard Race,3 and Bruce Chesebro3
Author affiliations: Rocky Mountain Laboratories, Hamilton, Montana, USA (B. Race, K.D. Meade-White, K.D. Barbian, C. Favara, D. Gardner, D. Long, M. Parnell, J. Striebel, S.A. Priola, A. Ward, R. Race, B. Chesebro); Colorado Division of Wildlife, Fort Collins, Colorado, USA (M.W. Miller); State University of New York Downstate Medical Center, Brooklyn, New York, USA (R. Rubenstein); New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA (G. LaFauci); American Red Cross, Rockville, Maryland, USA (L. Cervenakova); and University of Wyoming, Laramie, Wyoming, USA (E.S. Williams)

Suggested citation for this article

Abstract
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility. CWD was inoculated into these 2 species by intracerebral and oral routes. After intracerebral inoculation of squirrel monkeys, 7 of 8 CWD isolates induced a clinical wasting syndrome within 33–53 months. The monkeys' brains showed spongiform encephalopathy and protease-resistant prion protein (PrPres) diagnostic of prion disease. After oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes at 69 months postinfection. In contrast, cynomolgus macaques have not shown evidence of clinical disease as of 70 months postinfection. Thus, these 2 species differed in susceptibility to CWD. Because humans are evolutionarily closer to macaques than to squirrel monkeys, they may also be resistant to CWD.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative diseases that affect many mammalian species. Some examples include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, Creutzfeldt-Jakob disease (CJD) in humans, and chronic wasting disease (CWD) in cervids. CWD was first found in captive deer in Colorado in 1967 (1) and was later identified in several US states and Canadian provinces (2). Epidemiologic evidence suggests that CWD continues to spread among cervid populations in North America (3), creating concern that CWD may cross species barriers to infect humans or domestic animals that may be eaten by humans. Thus, the host range of CWD and the level of protection provided by species barriers should be determined.

Substantial progress has been made in testing species barriers for CWD by using transgenic mice expressing species-specific prion protein (PrP), by direct infection into new species, or by in vitro conversion assays. The most sensitive method for testing susceptibility to TSE agents is intracerebral injection. Unfortunately, this route does not mimic most natural situations and only enables assessment of whether the possibility of transmission exists. Hamir et al. infected cattle and sheep with CWD by the intracerebral route and found protease-resistant PrP (PrPres) in 5 of 13 cattle and 2 of 8 sheep, which indicated that these ruminant species can propagate CWD (4,5). However, oral exposure in these hosts apparently does not cause disease (2).

CWD cross-species transmission to nonagricultural and laboratory animals has shown variable levels of susceptibility depending on the route of transmission. For example, ferrets were 100% susceptible to CWD by intracerebral infection but were not susceptible to oral infection (6,7). Mink were only 25% susceptible to CWD by intracerebral infection and were not susceptible to oral infection (8). CWD has been successfully transmitted and adapted to laboratory rodents, including hamsters, transgenic mice expressing hamster PrP, and transgenic mice overexpressing mouse PrP (9,10). In contrast, transgenic mice expressing human PrP were not susceptible to CWD by intracerebral infection (11,12), a finding that provided evidence for a human species barrier against CWD infection. However, work started in 1980 and published in 2005 by Marsh et al. showed that 2 squirrel monkeys (Saimiri sciureus) infected by the intracerebral route with brain homogenate from a single CWD-affected mule deer became clinically sick at 31 and 34 months postinfection, and both were positive for PrPres (13). This evidence that at least 1 species of nonhuman primate was susceptible to CWD weakened the conclusion that humans may be protected from CWD by a species barrier.

We addressed 4 questions raised by the original observation that squirrel monkeys are susceptible to CWD (13). First, we compared intracerebral and oral routes of infection. This comparison was of interest because the oral route is likely to be an important natural route of disease transmission, and susceptibility is known to be lower by this route in most models. Second, we compared 2 species of nonhuman primates, cynomolgus macaques (Macaca fascicularis) and squirrel monkeys, each of which has previously shown susceptibility to various human prion diseases (14–16). However, humans are believed to be evolutionarily closer to cynomolgus macaques than to squirrel monkeys (17), and cynomolgus macaques may be a more accurate model for a human species barrier. Third, because only 1 CWD source was tested by Marsh et al. (13), we studied 8 different pools of CWD representing wild and captive cervids, including mule deer, white-tailed deer, and elk, from separate regions in the United States. Fourth, we tested the species tropism of CWD agent passaged in squirrel monkeys.

Suggested Citation for this Article

Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis [serial on the Internet]. 2009 Sep [date cited]. Available from http://www.cdc.gov/EID/content/15/9/1366.htm

DOI: 10.3201/eid1509.090253

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Susceptibilities of Nonhuman Primates to CWD | CDC EID