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. 1996 Dec;70(12):9064–9068. doi: 10.1128/jvi.70.12.9064-9068.1996

Human chromosome 6- and 11-encoded factors support human immunodeficiency virus type 1 Rev function in A9 cells.

R R Shukla 1, S M Marques 1, P L Kimmel 1, A Kumar 1
PMCID: PMC191013  PMID: 8971045

Abstract

The precise mechanism of Rev-mediated expression of human immunodeficiency virus (HIV-1) late genes is not well characterized. We recently proposed a requirement for HIV-1 Rev responsive element (RRE) RNA binding host nuclear proteins in Rev function. In this report, using a transient transfection assay of Rev function, we further demonstrate the role of host cell factors in HIV-1 Rev function. Murine A9 cells, which are inefficient in forming RRE-host protein ribonucleoprotein complexes, are also inefficient in supporting Rev function. We also show that host cell factor(s) encoded by human chromosomes 6 and 11 can support HIV-1 Rev-mediated expression of unspliced viral mRNAs in murine A9 cells.

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Selected References

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  1. Antoni B. A., Stein S. B., Rabson A. B. Regulation of human immunodeficiency virus infection: implications for pathogenesis. Adv Virus Res. 1994;43:53–145. doi: 10.1016/s0065-3527(08)60047-0. [DOI] [PubMed] [Google Scholar]
  2. Arrigo S. J., Chen I. S. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. Genes Dev. 1991 May;5(5):808–819. doi: 10.1101/gad.5.5.808. [DOI] [PubMed] [Google Scholar]
  3. Bogerd H. P., Fridell R. A., Madore S., Cullen B. R. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell. 1995 Aug 11;82(3):485–494. doi: 10.1016/0092-8674(95)90437-9. [DOI] [PubMed] [Google Scholar]
  4. Böhnlein S., Pirker F. P., Hofer L., Zimmermann K., Bachmayer H., Böhnlein E., Hauber J. Transdominant repressors for human T-cell leukemia virus type I rex and human immunodeficiency virus type 1 rev function. J Virol. 1991 Jan;65(1):81–88. doi: 10.1128/jvi.65.1.81-88.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang D. D., Sharp P. A. Messenger RNA transport and HIV rev regulation. Science. 1990 Aug 10;249(4969):614–615. doi: 10.1126/science.2143313. [DOI] [PubMed] [Google Scholar]
  6. Clawson G. A., Song Y. L., Schwartz A. M., Shukla R. R., Patel S. G., Connor L., Blankenship L., Hatem C., Kumar A. Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity. Cell Growth Differ. 1991 Nov;2(11):575–582. [PubMed] [Google Scholar]
  7. Cullen B. R., Malim M. H. The HIV-1 Rev protein: prototype of a novel class of eukaryotic post-transcriptional regulators. Trends Biochem Sci. 1991 Sep;16(9):346–350. doi: 10.1016/0968-0004(91)90141-h. [DOI] [PubMed] [Google Scholar]
  8. D'Agostino D. M., Felber B. K., Harrison J. E., Pavlakis G. N. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs. Mol Cell Biol. 1992 Mar;12(3):1375–1386. doi: 10.1128/mcb.12.3.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dayton E. T., Powell D. M., Dayton A. I. Functional analysis of CAR, the target sequence for the Rev protein of HIV-1. Science. 1989 Dec 22;246(4937):1625–1629. doi: 10.1126/science.2688093. [DOI] [PubMed] [Google Scholar]
  10. Felber B. K., Hadzopoulou-Cladaras M., Cladaras C., Copeland T., Pavlakis G. N. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495–1499. doi: 10.1073/pnas.86.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fischer U., Huber J., Boelens W. C., Mattaj I. W., Lührmann R. The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell. 1995 Aug 11;82(3):475–483. doi: 10.1016/0092-8674(95)90436-0. [DOI] [PubMed] [Google Scholar]
  12. Fischer U., Meyer S., Teufel M., Heckel C., Lührmann R., Rautmann G. Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J. 1994 Sep 1;13(17):4105–4112. doi: 10.1002/j.1460-2075.1994.tb06728.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fritz C. C., Zapp M. L., Green M. R. A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature. 1995 Aug 10;376(6540):530–533. doi: 10.1038/376530a0. [DOI] [PubMed] [Google Scholar]
  14. Greene W. C. The molecular biology of human immunodeficiency virus type 1 infection. N Engl J Med. 1991 Jan 31;324(5):308–317. doi: 10.1056/NEJM199101313240506. [DOI] [PubMed] [Google Scholar]
  15. Hart C. E., Ou C. Y., Galphin J. C., Moore J., Bacheler L. T., Wasmuth J. J., Petteway S. R., Jr, Schochetman G. Human chromosome 12 is required for elevated HIV-1 expression in human-hamster hybrid cells. Science. 1989 Oct 27;246(4929):488–491. doi: 10.1126/science.2683071. [DOI] [PubMed] [Google Scholar]
  16. Heaphy S., Dingwall C., Ernberg I., Gait M. J., Green S. M., Karn J., Lowe A. D., Singh M., Skinner M. A. HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region. Cell. 1990 Feb 23;60(4):685–693. doi: 10.1016/0092-8674(90)90671-z. [DOI] [PubMed] [Google Scholar]
  17. Hope T. J., Bond B. L., McDonald D., Klein N. P., Parslow T. G. Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif. J Virol. 1991 Nov;65(11):6001–6007. doi: 10.1128/jvi.65.11.6001-6007.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hope T. J., Huang X. J., McDonald D., Parslow T. G. Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787–7791. doi: 10.1073/pnas.87.19.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hope T. J., Klein N. P., Elder M. E., Parslow T. G. trans-dominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes. J Virol. 1992 Apr;66(4):1849–1855. doi: 10.1128/jvi.66.4.1849-1855.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hope T. J., McDonald D., Huang X. J., Low J., Parslow T. G. Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator: essential residues near the amino terminus. J Virol. 1990 Nov;64(11):5360–5366. doi: 10.1128/jvi.64.11.5360-5366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hope T., Pomerantz R. J. The human immunodeficiency virus type 1 Rev protein: a pivotal protein in the viral life cycle. Curr Top Microbiol Immunol. 1995;193:91–105. doi: 10.1007/978-3-642-78929-8_5. [DOI] [PubMed] [Google Scholar]
  22. Ivey-Hoyle M., Rosenberg M. Rev-dependent expression of human immunodeficiency virus type 1 gp160 in Drosophila melanogaster cells. Mol Cell Biol. 1990 Dec;10(12):6152–6159. doi: 10.1128/mcb.10.12.6152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kjems J., Frankel A. D., Sharp P. A. Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev. Cell. 1991 Oct 4;67(1):169–178. doi: 10.1016/0092-8674(91)90580-r. [DOI] [PubMed] [Google Scholar]
  25. Lu X. B., Heimer J., Rekosh D., Hammarskjöld M. L. U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7598–7602. doi: 10.1073/pnas.87.19.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Luo Y., Yu H., Peterlin B. M. Cellular protein modulates effects of human immunodeficiency virus type 1 Rev. J Virol. 1994 Jun;68(6):3850–3856. doi: 10.1128/jvi.68.6.3850-3856.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Malim M. H., Tiley L. S., McCarn D. F., Rusche J. R., Hauber J., Cullen B. R. HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. Cell. 1990 Feb 23;60(4):675–683. doi: 10.1016/0092-8674(90)90670-a. [DOI] [PubMed] [Google Scholar]
  28. Neumann M., Felber B. K., Kleinschmidt A., Froese B., Erfle V., Pavlakis G. N., Brack-Werner R. Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. J Virol. 1995 Apr;69(4):2159–2167. doi: 10.1128/jvi.69.4.2159-2167.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Newstein M., Stanbridge E. J., Casey G., Shank P. R. Human chromosome 12 encodes a species-specific factor which increases human immunodeficiency virus type 1 tat-mediated trans activation in rodent cells. J Virol. 1990 Sep;64(9):4565–4567. doi: 10.1128/jvi.64.9.4565-4567.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pomerantz R. J., Trono D., Feinberg M. B., Baltimore D. Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency. Cell. 1990 Jun 29;61(7):1271–1276. doi: 10.1016/0092-8674(90)90691-7. [DOI] [PubMed] [Google Scholar]
  31. Rosen C. A. Regulation of HIV gene expression by RNA-protein interactions. Trends Genet. 1991 Jan;7(1):9–14. doi: 10.1016/0168-9525(91)90015-i. [DOI] [PubMed] [Google Scholar]
  32. Rosen C. A. Tat and Rev: positive modulators of human immunodeficiency virus gene expression. Gene Expr. 1991 May;1(2):85–90. [PMC free article] [PubMed] [Google Scholar]
  33. Shukla R. R., Kimmel P. L., Kumar A. Human immunodeficiency virus type 1 Rev-responsive element RNA binds to host cell-specific proteins. J Virol. 1994 Apr;68(4):2224–2229. doi: 10.1128/jvi.68.4.2224-2229.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shukla R. R., Kumar A., Kimmel P. L. Transforming growth factor beta increases the expression of HIV-1 gene in transfected human mesangial cells. Kidney Int. 1993 Nov;44(5):1022–1029. doi: 10.1038/ki.1993.344. [DOI] [PubMed] [Google Scholar]
  35. Stauber R., Gaitanaris G. A., Pavlakis G. N. Analysis of trafficking of Rev and transdominant Rev proteins in living cells using green fluorescent protein fusions: transdominant Rev blocks the export of Rev from the nucleus to the cytoplasm. Virology. 1995 Nov 10;213(2):439–449. doi: 10.1006/viro.1995.0016. [DOI] [PubMed] [Google Scholar]
  36. Stutz F., Neville M., Rosbash M. Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell. 1995 Aug 11;82(3):495–506. doi: 10.1016/0092-8674(95)90438-7. [DOI] [PubMed] [Google Scholar]
  37. Stutz F., Rosbash M. A functional interaction between Rev and yeast pre-mRNA is related to splicing complex formation. EMBO J. 1994 Sep 1;13(17):4096–4104. doi: 10.1002/j.1460-2075.1994.tb06727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vaishnav Y. N., Wong-Staal F. The biochemistry of AIDS. Annu Rev Biochem. 1991;60:577–630. doi: 10.1146/annurev.bi.60.070191.003045. [DOI] [PubMed] [Google Scholar]
  39. Winslow B. J., Trono D. The blocks to human immunodeficiency virus type 1 Tat and Rev functions in mouse cell lines are independent. J Virol. 1993 Apr;67(4):2349–2354. doi: 10.1128/jvi.67.4.2349-2354.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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