Abstract

For the past 20 years or more, retroviruses have proven to be highly rewarding objects of study, and have provided new and important insights into fundamental aspects of eukaryotic molecular biology, gene organization, genetics, and oncogenesis. The goal of this proposal is to continue our studies in several key areas of molecular retrovirology emphasizing avian and murine retroviral models. Areas of emphasis include the following: 1) The structure and function of ALV env proteins and their receptors as well as mechanisms of viral entry and superinfection resistance; 2) The specificity and mechanism of viral DNA integration and the role of DNA structure and DNA-associated proteins in this process; 3) The mechanisms underlying the extraordinary genetic and biological diversity characteristic of retroviruses, including mechanisms of legitimate and illegitimate recombination and the role and power of selective influences in molding the viral genome; 4) The evolution of endogenous retroviruses and the use of these elements to study genetics and evolution of their hosts; 5) The role of superantigen activity in the replication of MMTV and the evolution of these viruses and their host.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA044385-11
Application #
2442960
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1987-09-04
Project End
2001-06-30
Budget Start
1997-09-01
Budget End
1998-06-30
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

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
Rouzine, I M; Coffin, J M (1999) Linkage disequilibrium test implies a large effective population number for HIV in vivo. Proc Natl Acad Sci U S A 96:10758-63
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

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