Over the last two decades retroviruses have served as important and productive objects of study. Experiments with retroviruses have yielded fundamental results in molecular oncology as well as mechanisms of information transfer and gene structure and expression in eukaryotic cells. Considering the recent recognition of retroviruses as important human pathogens, as well as the continuing revelation of non viral elements that appear to use similar mechanisms, it is certain that study of these agents on the molecular level will continue to be highly rewarding. The goals of this project are to continue our study of several fundamental aspects of retrovirus biology on the molecular level in order to obtain a deeper understanding of the virus-cell interaction. Areas of study include 1) the structure and function of the viral envelope protein and its cellular receptor; 2) structure of the major core protein precursor and its role in assembly; 3) mechanism of integration of the viral DNA into the DNA of the host cells; 4) mechanisms of expression of the provirus and dissection of signals which specify synthesis and processing of viral RNA; and 5) descriptions of the interactions of endogenous viruses with the host species. It is hoped that these studies will provide novel insights into important and unique features of these fascinating entities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
1R35CA044385-01
Application #
3479608
Study Section
(SRC)
Project Start
1987-09-04
Project End
1994-08-31
Budget Start
1987-09-04
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Rouzine, I M; Coffin, J M (2005) Evolution of human immunodeficiency virus under selection and weak recombination. Genetics 170:7-18
Rouzine, Igor M; Wakeley, John; Coffin, John M (2003) The solitary wave of asexual evolution. Proc Natl Acad Sci U S A 100:587-92
Rainey, G Jonah A; Natonson, Andrew; Maxfield, Lori F et al. (2003) Mechanisms of avian retroviral host range extension. J Virol 77:6709-19
Hughes, J F; Coffin, J M (2001) Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29:487-9
Rouzine, I M; Rodrigo, A; Coffin, J M (2001) Transition between stochastic evolution and deterministic evolution in the presence of selection: general theory and application to virology. Microbiol Mol Biol Rev 65:151-85
Zhou, H; Rainey, G J; Wong, S K et al. (2001) Substrate sequence selection by retroviral integrase. J Virol 75:1359-70
Tovar Sepulveda, V A; Berdel, B; Coffin, J M et al. (2000) Mouse mammary tumor virus superantigen expression is reduced by glucocorticoid treatment. Virology 275:98-106
Reuss, F U; Coffin, J M (2000) The mouse mammary tumor virus transcription enhancers for hematopoietic progenitor and mammary gland cells share functional elements. J Virol 74:8183-7
Tomonaga, K; Coffin, J M (1999) Structures of endogenous nonecotropic murine leukemia virus (MLV) long terminal repeats in wild mice: implication for evolution of MLVs. J Virol 73:4327-40
Johnson, W E; Coffin, J M (1999) Constructing primate phylogenies from ancient retrovirus sequences. Proc Natl Acad Sci U S A 96:10254-60

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