Department / Division Affiliations
|Vice Chair, and Professor, Molecular & Medical Pharmacology|
|Member, Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC)|
Retroviruses are RNA viruses that replicate through a DNA intermediate. In humans, infection by retroviruses can lead to AIDS, lymphoma, and leukemia. My present studies focus on understanding the molecular mechanisms of the integration reaction catalyzed by the viral protein, integrase, purified from the human immunodeficiency virus (HIV), and examining possible chromosomal instability as a result of retroviral integration. Owing to their integration properties, retroviruses are also widely used as vectors for genetic engineering and gene replacement therapy. Progress in understanding the mechanism of integration may lead to development of still more powerful tools for molecular medicine. A related project is aimed at introducing exogenous DNA into specific target sites by use of fusion proteins consisting of HIV integrase and sequence-specific DNA binding proteins. Other research interests include feline immunodeficiency virus (FIV) and the development of FIV infection in cats as a model for HIV infection and anti-retroviral therapy in humans.
For more detailed information, please visit the lab website.
Dobard, C.W., Briones, M. and Chow, S.A. Molecular mechanisms by which HIV-1 integrase stimulates the early steps of reverse transcription. J Virol 2007; 81: 10037-10046.
Dong, B., Kim, S., Hong, S., Das Gupta, J., Malathi, K., Klein, E.A., Ganem, D., DeRisi, J., Chow, S.A. and Silverman, R.H. An infectious retrovirus susceptible to an interferon antiviral pathway from human prostate tumors. Pro Natl Acad Sci USA 2007; 104(5): 1655-1660.
Vatakis, D.N., Bristol, G., Wilkinson, T.A., Chow, S.A. and Zack, J.A. Immediate activation to rescue efficient HIV replication in quiescent CD4+ T cells. J Virol 2007; 81: 3574-3582.
Kim, S. Kim, Y. Liang, T. Sinsheimer, J. S. Chow, S. A. A high-throughput method for cloning and sequencing human immunodeficiency virus type 1 integration sites. J Virol. 2006; 80(22): 11313-21.
Tan, W. Dong, Z. Wilkinson, T. A. Barbas, C. F., 3rd Chow, S. A. Human immunodeficiency virus type 1 incorporated with fusion proteins consisting of integrase and the designed polydactyl zinc finger protein E2C can bias integration of viral DNA into a predetermined chromosomal region in human cells. J Virol. 2006; 80(4): 1939-48.
Brooks, D. G. Cohen, M. D. Jamieson, B. D. Poon, B. Kitchen, S. G. Chow, S. A. Chen, I. S. Zack, J. A. Koka, P. S. Rapid size dependent deletion of foreign gene sequences inserted into attenuated HIV-1 upon infection in vivo: implications for vaccine development. Curr HIV Res. 2005; 3(4): 377-92.
Tan, W. Zhu, K. Segal, D. J. Barbas, C. F., 3rd Chow, S. A. Fusion proteins consisting of human immunodeficiency virus type 1 integrase and the designed polydactyl zinc finger protein E2C direct integration of viral DNA into specific sites. J Virol. 2004; 78(3): 1301-13.
Zhu, K. Dobard, C. Chow, S. A. Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J Virol. 2004; 78(10): 5045-55.
Wilkinson, T.A, Tan, W. and Chow, S.A. Safe delivery of therapeutic genes into specific chromosomal sites using engineered retroviral integrase. Gene Ther. Regulation 2004; 2(4): 369-387.
Woodward CL, Wang Y, Dixon WJ, Htun H, Chow SA Subcellular localization of feline immunodeficiency virus integrase and mapping of its karyophilic determinant. J Virol . 2003; 77(8): 4516-27.
Holmes-Son ML, Chow SA Correct integration mediated by integrase-LexA fusion proteins incorporated into HIV-1. Mol Ther. 2002; 5(4): 360-70.
Holmes-Son ML, Appa RS, Chow SA Molecular genetics and target site specificity of retroviral integration. Adv Genet . 2001; 43: 33-69.
Appa RS, Shin C-G, Lee P, Chow SA Role of the nonspecific DNA-binding region and a-helices within the core domain of retroviral integrase in selecting target DNA sites for integration. J Biol Chem 2001; 276: 45848-45855.
Holmes-Son ML, Chow SA Integrase-lexA fusion proteins incorporated into human immunodeficiency virus type 1 that contains a catalytically inactive integrase gene are functional to mediate integration. J Virol . 2000; 74(24): 11548-56.
Zhu K, Cordeiro ML, Atienza J, Robinson WE, Chow SA Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids. J Virol . 1999; 73(4): 3309-16.
Wong BC, Chiu SK, Chow SA The role of negative superhelicity and length of homology in the formation of paranemic joints promoted by RecA protein. J Biol Chem. 1998; 273(20): 12120-7.
Shibagaki Y, Chow SA Central core domain of retroviral integrase is responsible for target site selection. J Biol Chem 1997; 272: 8361-8369.
Shibagaki Y, Holmes ML, Appa RS, Chow SA Characterization of feline immunodeficiency virus integrase and analysis of functional domains. Virology . 1997; 230(1): 1-10.
Scottoline BP, Chow S, Ellison V, Brown PO Disruption of the terminal base pairs of retroviral DNA during integration. Genes Dev . 1997; 11(3): 371-82.
Chow SA In vitro assays for activities of retroviral integrase. Methods: a Companion to Methods in Enzymology 1997; 12: 306-317.
Robinson WE, Cordeiro M, Abdel-Malek S, Jia Q, Chow SA, Reinecke MG, Mitchell WM Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase. Mol Pharmacol . 1996; 50(4): 846-55.
Goulaouic H, Chow SA Directed integration of viral DNA mediated by fusion proteins consisting of human immunodeficiency virus type 1 integrase and Escherichia coli LexA protein. J Virol . 1996; 70(1): 37-46.
Robinson Jr. WE, Reinicke MG, Abdel-Malek S, Jia Q, Chow SA Inhibitors of HIV-1 replication that inhibit HIV integrase. Proc Natl Acad Sci USA 1996; 93: 6326-6331.
Chow SA, Brown PO Substrate features important for recognition and catalysis by human immunodeficiency virus type 1 integrase identified by using novel DNA substrates. J Virol . 1994; 68(6): 3896-907.
Chow SA, Chiu SK, Wong BC RecA protein-promoted homologous pairing and strand exchange between intact and partially single-stranded duplex DNA. J Mol Biol . 1992; 223(1): 79-93.
Chow SA, Vincent KA, Ellison V, Brown PO Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science 1992; 255: 723-726.
Vatakis, D. N. Kim, S. Kim, N. Chow, S. A. Zack, J. A. Human immunodeficiency virus integration efficiency and site selection in quiescent CD4+ T cells. J. Virol. 2009; 83(12): 6222-6533.
Woodward, C. L. Prakobwanakit, S. Mosessian, S. Chow, S. A. Integrase interacts with nucleoporin NUP153 to mediate the nuclear import of human immunodeficiency virus type 1. J. Virol. 2009; 83(13): 6522-6533.
Su, K. Wang, D. Ye, J. Kim, Y. C. Chow, S. A. Site-specific integration of retroviral DNA in human cells using fusion proteins consisting of human immunodeficiency virus type 1 integrase and the designed polydactyl zinc-finger protein E2C. Methods. 2009; 47(4): 269-276.
Kim, S. Kim, N. Dong, B. Boren, D. Lee, S. A. Das Gupta, J. Gaughan, C. Klein, E. A. Lee, C. Silverman, R. H. Chow, S. A. Integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer. J. Virol 2008; 82(20): 9964-9977.
Wilkinson, T. A. Januszyk, K. Phillips, M. L. Tekeste, S. S. Zhang, M. Miller, J. T. Le Grice, S. F. Clubb, R. T. Chow, S. A. Identifying and Characterizing a Functional HIV-1 Reverse Transcriptase-binding Site on Integrase. J. Biol. Chem. 2009; 284(12): 7931-7939.