Leonard H. Evans, Ph.D.
Chief, Retroviral Molecular Biology Section
Senior Investigator
Retroviral Molecular Biology Section
Dr. Evans received his Ph.D. in biochemistry in 1977 at the Oregon Health Sciences University in Portland, OR. He did postdoctoral studies on the genetic structure of retroviruses in the Department of Molecular and Cellular Biology at the University of California at Berkeley from 1977 until 1980. In 1980, he joined the Rocky Mountain Laboratories, where he is currently a senior investigator in the Laboratory of Persistent Viral Diseases.
Description of Research Program
A major focus of our laboratory is the effect of mixed retrovirus infections on viral replication and pathology in the host. Mixed infections can result from infection with a heterogeneous population of viruses or by genetic alterations of retroviruses, such as point mutations or recombination that may occur subsequent to infection.
Much of our research has concerned the interactions of inoculated retroviruses (exogenous retroviruses) with their endogenous counterparts in mice in an effort to elucidate some of the general principals of in vivo retroviral interactions. Upon infection, exogenous mouse retroviruses undergo recombination with endogenous retroviruses to generate variants with different infectious properties. Our studies involve the characterization of the endogenous viruses, the mechanism of recombination of the endogenous viruses with exogenous viruses, and the effect of the resulting mixed infection on pathogenesis.
In another approach to mixed retrovirus infections, we have studied the co-inoculation of mixtures of retroviruses. In recent studies, we have found that inoculation of two nonpathogenic retroviruses as a mixture induces a neurological disease in mice which ranks as one of the most rapidly progressive retroviral diseases ever observed.
Considering that all mammals harbor a very large number of retroviruses in their genomes, infection of mammals by any exogenous retrovirus may be considered to result in a mixed retrovirus infection. Approximately 8% of the genomes of mammals, including humans and mice, are composed of retroviral elements acquired by infection of germ line cells during the course of evolution. Retroviral insertions in our genome number about 40,000 and are in the same range as the total number of genes encoded by our DNA. The impact of endogenous retrovirus insertions on evolution and the extent to which functional retroviral elements have been utilized in our own physiological processes is an emerging area of study.
In this regard, although most of the endogenous retroviruses are defective and, for the most part, quiescent, some appear to be intact. Several contain one or more intact viral genes that are expressed during development and certain physiological or pathological conditions. The expression of endogenous retroviruses and their control is not well understood. Our recent characterization of endogenous retroviruses in mice has enabled us to initiate studies examining the detailed expression of the endogenous retroviruses during development. In addition, we are examining the effects of exogenous retrovirus infection on the expression and mobilization of endogenous retroviruses.
Research Group Members
Lukas Swanson, Postbaccalaureate IRTA Fellow; Frank Malik, Biological Science Lab Technician.
Selected Recent Publications
Alamgir ASM, Owens N, Lavignon M, Malik F, Evans LH. Precise identification of endogenous proviruses of NFS/N mice participating in recombination with Moloney ecotropic MuLV to generate polytropic MuLVs. J Virol. 2005. 79(8): 4664-71.
Peterson KE, Errett JS, Wei T, Dimcheff DE, Ransohoff R, Kuziel WA, Evans L, Chesebro B. MCP-1 and CCR2 contribute to non-lymphocyte-mediated brain disease induced by Fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral neuropathogenesis. J Virol. 2004. 78(12): 6449-58.
Dittmer U, He H, Messer RJ, Schimmer S, Olbrich AR, Ohlen C, Greenberg PD, Stromnes IM, Iwashiro M, Sakaguchi S, Evans LH, Peterson KE, Yang G, Hasenkrug KJ. Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection. Immunity. 2004. 20(3): 293-303.
Evans LH, Lavignon M, Taylor M, Alamgir AS. Antigenic subclasses of polytropic murine leukemia virus (MLV) isolates reflect three distinct groups of endogenous polytropic MLV-related sequences in NFS/N mice. J Virol. 2003. 77(19): 10327-38.
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