The specific aim of this research proposal is an understanding of the roles of the various avian retrovirus genomic regions in viral replication and transformation. This will be accomplished by biochemical analyses of nonconditional mutants of Rous sarcoma virus. These include mutants in env and pol as well as in a mutant lacking sequences necessary for genomic RNA packaging. These mutants will also be utilized in order to investigate recombination between host and viral sequences and the generation of new transforming viruses. These studies will be important in understanding the generation of transforming sequences from normal cellular genes. In addition, we are commencing work on the isolation of mutants of acute leukemia viruses which transform myeloid lineage cells. The target cell specificity of the transforming sequences of these viruses will be explored. These studies will aid in development of a model of evolution of and oncogenesis by retroviruses with different transforming sequences.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Virology Study Section (VR)
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Fred Hutchinson Cancer Research Center
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Matsen 4th, Frederick A; Small, Christopher T; Soliven, Khanh et al. (2014) A novel Bayesian method for detection of APOBEC3-mediated hypermutation and its application to zoonotic transmission of simian foamy viruses. PLoS Comput Biol 10:e1003493
Stenbak, Carolyn R; Craig, Karen L; Ivanov, Sergei B et al. (2014) New World simian foamy virus infections in vivo and in vitro. J Virol 88:982-91
Feeroz, Mostafa M; Soliven, Khanh; Small, Christopher T et al. (2013) Population dynamics of rhesus macaques and associated foamy virus in Bangladesh. Emerg Microbes Infect 2:e29
Lee, Eun-Gyung; Stenbak, Carolyn R; Linial, Maxine L (2013) Foamy virus assembly with emphasis on pol encapsidation. Viruses 5:886-900
Jackson, Dana L; Lee, Eun-Gyung; Linial, Maxine L (2013) Expression of prototype foamy virus pol as a Gag-Pol fusion protein does not change the timing of reverse transcription. J Virol 87:1252-4
Soliven, Khanh; Wang, Xiaoxing; Small, Christopher T et al. (2013) Simian foamy virus infection of rhesus macaques in Bangladesh: relationship of latent proviruses and transcriptionally active viruses. J Virol 87:13628-39
Lee, Eun-Gyung; Sinicrope, Amber; Jackson, Dana L et al. (2012) Foamy virus Pol protein expressed as a Gag-Pol fusion retains enzymatic activities, allowing for infectious virus production. J Virol 86:5992-6001
Yu, Shuyuarn F; Lujan, Phillip; Jackson, Dana L et al. (2011) The DEAD-box RNA helicase DDX6 is required for efficient encapsidation of a retroviral genome. PLoS Pathog 7:e1002303
Lee, Eun-Gyung; Roy, Jacqueline; Jackson, Dana et al. (2011) Foamy retrovirus integrase contains a Pol dimerization domain required for protease activation. J Virol 85:1655-61
Lee, Eun-Gyung; Kuppers, Daniel; Horn, Megan et al. (2008) A premature termination codon mutation at the C terminus of foamy virus Gag downregulates the levels of spliced pol mRNA. J Virol 82:1656-64

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