John L. Portis, M.D.
Chief, Retroviral Neuropathogenesis Section
Senior Investigator
Retroviral Neuropathogenesis Section
Dr. Portis received his M.D. in 1971 from the UCLA School of Medicine, where he also completed his residency training in pathology. He joined the Rocky Mountain Laboratories in 1976 and is a senior investigator in the Laboratory of Persistent Viral Diseases. His research interests focus on the virus/host interactions driving the neuropathologies induced by retroviral infection of the central nervous system. He is a faculty affiliate at the University of Montana and has participated in their graduate program.
Description of Research Program
This laboratory uses molecular biological approaches to study the pathogenesis of noninflammatory spongiform neurodegenerative diseases of mice that are caused by retroviruses. The goal is to understand, at the molecular level, the nature of retroviral neurovirulence.
Using DNA cloning techniques, we have mapped the viral sequences that are determinants of neuroinvasiveness and neurovirulence. We have also identified host factors that influence both the neuroinvasiveness and the neurovirulence of these viruses. Transcriptional profiling has revealed that the Unfolded Protein Response (UPR) is activated very early in the genesis of this disease. The UPR is an adaptive cellular response to endoplasmic reticulum (ER) stress, in this case induced by the accumulation of misfolded viral envelope protein. This disease, therefore, appears to represent a protein folding disease caused by a conventional virus.
Work in the laboratory is now focused on characterizing the specific biochemical pathways activated in the brains of infected mice and the cells in which these responses are activated. ER stress appears to be a feature of a variety of human neurodegenerative diseases, such as Alzheimer’s, familial forms of Parkinson’s, Huntington’s disease, and some forms of prion diseases, which all involve the accumulation of misfolded host proteins. It is anticipated that understanding the details of this viral disease of mice will provide clues of the role of protein-folding instability in the pathogenesis of these human diseases.
Research Group Members
Yearim Gutierrez-Cotto, Postbaccalaureate IRTA Fellow; Frank McAtee, M.S., Microbiologist SRA.
Selected Publications
To view a complete listing, visit PubMed.
Dimcheff DE, Faasse MA, McAtee FJ, Portis JL. Endoplasmic reticulum (ER) stress induced by a neurovirulent mouse retrovirus is associated with prolonged BiP binding and retention of a viral protein in the ER. J Biol Chem. 2004 Aug 6;279(32):33782-90.
Dimcheff DE, Askovic S, Baker AH, Johnson-Fowler C, Portis JL. Endoplasmic reticulum stress is a determinant of retrovirus-induced spongiform neurodegeneration. J Virol. 2003 Dec;77(23):12617-29.
Asković S, Favara C, McAtee FJ, Portis JL. Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus. J Virol. 2001 Mar;75(6):2665-74.
Asković S, McAtee FJ, Favara C, Portis JL. Brain infection by neuroinvasive but avirulent murine oncornaviruses. J Virol. 2000 Jan;74(1):465-73.
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