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 percent 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.
Dr. Evans received his Ph.D. in biochemistry in 1977 at the Oregon Health Sciences University in Portland. 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.
Rebecca Dewoody, Postdoctoral IRTA
Joyce Brewer, Postdoctoral IRTA
Erik VanDis, Post baccalaureate IRTA
Stefano Boi, Ph.D. Student
Frank Malik, Biological Science Lab Technician
Rosenke K, Lavignon M, Malik F, Kolokithas A, Hendrick D, Virtaneva K, Peterson K, Evans LH. Profound amplification of pathogenic murine polytropic retrovirus release from coinfected cells. J Virol. 2012 Jul;86(13):7241-8.
Leroy V, Kihara M, Baudino L, Brighouse G, Evans LH, Izui S. Sgp3 and TLR7 stimulation differentially alter the expression profile of modified polytropic retroviruses implicated in murine systemic lupus. J Autoimmun. 2012 Jun;38(4):361-8.
Smith DS, Guo K, Barrett BS, Heilman KJ, Evans LH, Hasenkrug KJ, Greene WC, Santiago ML. Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response. PLoS Pathog. 2011 Oct;7(10):e1002284.
Kihara M, Leroy V, Baudino L, Evans LH, Izui S. Sgp3 and Sgp4 control expression of distinct and restricted sets of xenotropic retroviruses encoding serum gp70 implicated in murine lupus nephritis. J Autoimmun. 2011 Dec;37(4):311-8.
Kolokithas A, Rosenke K, Malik F, Hendrick D, Swanson L, Santiago ML, Portis JL, Hasenkrug KJ, Evans LH. The glycosylated Gag protein of a murine leukemia virus inhibits the antiretroviral function of APOBEC3. J Virol. 2010 Oct;84(20):10933-6.
Baudino L, Yoshinobu K, Dunand-Sauthier I, Evans LH, Izui S. TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice. J Autoimmun. 2010 Sep;35(2):153-9.
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Evans LH, Britt WJ, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Versatile reagent for detecting murine leukemia viruses. United States patent US 6,709,811. 23 Mar 2004.
Last Updated October 18, 2012
Last Reviewed October 18, 2012