Abstract
Human integrase interactor 1 (INI1/SMARCB1/SNF5) is a chromatin-remodeling molecule that binds to HIV-1 integrase and enhances proviral DNA integration. INI1 is also known as a tumor suppressor gene and has been found to be mutated in several aggressive tumors such as rhabdoid and lymphoid tumors. To study the function of simian INI1, we screened and cloned simian INI1 cDNA from B lymphoma cells of rhesus monkeys using RT-PCR. Sequence analysis showed 23 single nucleotide differences compared to the human ortholog, which, however, did not result in amino acid changes, and the amino acid sequence is therefore 100 % conserved between human and simian INI1. Two alternatively spliced isoforms, INI1a and INI1b, were also found in simian INI1. These two isoforms did not show any functional difference in HIV-1 proviral DNA integration and nuclear localization, suggesting that the specificity of simian INI1 would not be a factor preventing HIV-1 infection of a simian host. Nevertheless, INI1b is expressed only in established cancer cell lines such as Jurkat and COS-7 cells, and not in primary cells, suggesting that INIlb could be an indicator of cell transformation.
References
Bruder CE, Dumanski JP, Kedra D (1999) The mouse ortholog of the human SMARCB1 gene encodes two splice forms. Biochem Biophys Res Commun 257:886–890
Das S, Cano J, Kalpana GV (2009) Multimerization and DNA binding properties of INI1/hSNF5 and its functional significance. J Biol Chem 284:19903–19914
Kalderon D, Richardson WD, Markham AF, Smith AE (1984) Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature 311:33–38
Kalpana GV, Marmon S, Wang W, Crabtree GR, Goff SP (1994) Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266:2002–2006
Kingston RE, Bunker CA, Imbalzano AN (1996) Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev 10:905–920
Lanford RE, Butel JS (1984) Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen. Cell 37:801–813
Park IW, Sodroski J (1995) Functional analysis of the vpx, vpr, and nef genes of simian immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 8:335–344
Pyeon D, Park IW (2015) Interaction between Nef and INI1/SMARCB1 augments replicability of HIV-1 in resting human peripheral blood mononuclear cells. Arch Virol 160:727–737
Roberts CW, Biegel JA (2009) The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer Biol Ther 8:412–416
Tsikitis M, Zhang Z, Edelman W, Zagzag D, Kalpana GV (2005) Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss. Proc Natl Acad Sci USA 102:12129–12134
Zhang ZK, Davies KP, Allen J, Zhu L, Pestell RG, Zagzag D, Kalpana GV (2002) Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5. Mol Cell Biol 22:5975–5988
Acknowledgments
This work was supported by the David Geffen Research Fellowship for AIDS Research (D. P.) and NIH/NIDDK R01 DK099055 (I-W. P).
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Pyeon, D., Price, L. & Park, IW. Comparative molecular genetic analysis of simian and human HIV-1 integrase interactor INI1/SMARCB1/SNF5. Arch Virol 160, 3085–3091 (2015). https://doi.org/10.1007/s00705-015-2585-x
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DOI: https://doi.org/10.1007/s00705-015-2585-x