Laboratory of Persistent Viral Diseases

Bruce W. Chesebro, M.D.

Chief, Laboratory of Persistent Viral Diseases
Chief, TSE/Prion and Retroviral Pathogenesis Section

Dr. Chesebro received his M.D. from Harvard Medical School in 1968. He completed postdoctoral studies at Karolinska Institute, 1967; Stanford University, 1968–1970; and National Institute of Arthritis and Metabolic Diseases, 1970–1972. He came to the Rocky Mountain Laboratories in 1972 and became the chief of the Laboratory of Persistent Viral Diseases in 1979.

Figure shows protease-resistant prion protein (PrP-res) deposited as amyloid stained with Thioflavin S in the corpus callosum and cerebellum of an anchorless PrP transgenic mouse 194 days after infection with scrapie strain 22L. Adapted from Chesebro et al. Science 308:1435-39, 2005.

Description of Research Program

Research is aimed at studying the pathogenesis of transmissible encephalopathies or prion diseases. These diseases are being studied at the biochemical, cellular, and whole animal model levels. We are currently studying both chronic wasting disease (CWD) of deer and elk as well as rodent-adapted sheep scrapie. Rodent and nonhuman primate models are being used for CWD. Mutant prion protein (PrP) molecules have been expressed in neural cell cultures and in transgenic mice to study the effects of PrP alterations on agent replication and disease development. Knockout mice that lack expression of important cytokine and chemokine genes and their receptors are also used for pathogenesis studies.

Our group also studies a transgenic mouse model expressing anchorless prion protein. This model replicates the prion/TSE agent and has extensive amyloid deposits in the brain with cerebral amyloid angiopathy similar to human brain amyloid diseases including Alzheimer’s disease. This model mimics a new fatal familial prion disease in which patients express prion protein with a stop codon near the C-terminus, thus eliminating the GPI anchoring of prion protein.

Research Group Members

James Striebel, M.S., Biologist; Mikael Klingeborn, Ph.D., Visiting Fellow; Deborah Tribouillard, Ph.D., Visiting Fellow; Alejandra Rangel, Ph.D., Visiting Fellow; Brent Race, D.V.M., Veterinary Staff Scientist; Kimberly Meade-White, M.S., Biologist; Melissa Pathmajeyan, Graduate Student.

Selected Publications

(View list in PubMed)

Chesebro B, Race B, Meade-White K, LaCasse R, Race R, Klingeborn M, Striebel J, Dorward D, McGovern G, Jeffrey M. Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathog. 2010, in press.

Tribouillard-Tanvier D., Striebel JF, Peterson KE, Chesebro B. Analysis of protein levels of 24 cytokines in scrapie agent-infected brain and glial cell cultures from mice differing in prion protein expression levels. J Virol. 2009; 83: 11244-11253.

Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, Cervenakova L, Favara C, Gardner D, Long D, Parnell M, Striebel J, Priola SA, Ward A, Williams ES, Race R, Chesebro B. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis. 2009; 15: 1366-1376.

Race B, Meade-White K, Oldstone MB, Race R, Chesebro B. Detection of prion infectivity in fat tissues of scrapie-infected mice. PLoS Pathog. 2008; December 4(12):e1000232. Epub.

Santiago ML, Montano M, Benitez R, Messer RJ, Yonemoto W, Chesebro B, Hasenkrug KJ, Greene WC. Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science. 2008; 321(5894):1343-1346.

Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E, Oldstone M. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science. 2005 Jun 3;308(5727):1435-9.

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