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. 1993 Apr;67(4):2349–2354. doi: 10.1128/jvi.67.4.2349-2354.1993

The blocks to human immunodeficiency virus type 1 Tat and Rev functions in mouse cell lines are independent.

B J Winslow 1, D Trono 1
PMCID: PMC240394  PMID: 8445733

Abstract

Rodent cells present two blocks precluding the expression of the human immunodeficiency virus type 1 (HIV-1) genome. First, the viral protein Tat is only poorly active in these cells. Second, when the HIV-1 provirus is integrated in the genome of mouse cells, it electively fails to express the viral structural proteins, indicating a block to Rev action. Both defects can be complemented by fusion of the infected mouse cells with uninfected human cells. Because the production of high levels of Rev is dependent on Tat-mediated transactivation and because both Tat and Rev bind the viral transcript, it has been hypothesized that the two blocks found in rodent cells might be linked. In the present work, we demonstrate that overexpression of Rev in mouse cell lines does not relieve their block in HIV-1 structural-gene expression. In addition, we show that this defect is also present in human-mouse cell hybrids which contain human chromosome 12 and support Tat function. On that basis, we conclude that the blocks to HIV-1 Tat and Rev action in mouse cell lines are independent and result from the absence of distinct cellular elements that are critical for HIV-1 gene expression.

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Selected References

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  1. Alonso A., Derse D., Peterlin B. M. Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells. J Virol. 1992 Jul;66(7):4617–4621. doi: 10.1128/jvi.66.7.4617-4621.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berberich S. L., Macias M., Zhang L., Turek L. P., Stoltzfus C. M. Comparison of Rous sarcoma virus RNA processing in chicken and mouse fibroblasts: evidence for double-spliced RNA in nonpermissive mouse cells. J Virol. 1990 Sep;64(9):4313–4320. doi: 10.1128/jvi.64.9.4313-4320.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang D. D., Sharp P. A. Regulation by HIV Rev depends upon recognition of splice sites. Cell. 1989 Dec 1;59(5):789–795. doi: 10.1016/0092-8674(89)90602-8. [DOI] [PubMed] [Google Scholar]
  4. Cochrane A. W., Jones K. S., Beidas S., Dillon P. J., Skalka A. M., Rosen C. A. Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression. J Virol. 1991 Oct;65(10):5305–5313. doi: 10.1128/jvi.65.10.5305-5313.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dayton A. I., Terwilliger E. F., Potz J., Kowalski M., Sodroski J. G., Haseltine W. A. Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J Acquir Immune Defic Syndr. 1988;1(5):441–452. [PubMed] [Google Scholar]
  6. Fu X. D., Katz R. A., Skalka A. M., Maniatis T. The role of branchpoint and 3'-exon sequences in the control of balanced splicing of avian retrovirus RNA. Genes Dev. 1991 Feb;5(2):211–220. doi: 10.1101/gad.5.2.211. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Jolicoeur P., Laperrière A., Beaulieu N. Efficient production of human immunodeficiency virus proteins in transgenic mice. J Virol. 1992 Jun;66(6):3904–3908. doi: 10.1128/jvi.66.6.3904-3908.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Katz R. A., Skalka A. M. Control of retroviral RNA splicing through maintenance of suboptimal processing signals. Mol Cell Biol. 1990 Feb;10(2):696–704. doi: 10.1128/mcb.10.2.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Landau N. R., Warton M., Littman D. R. The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature. 1988 Jul 14;334(6178):159–162. doi: 10.1038/334159a0. [DOI] [PubMed] [Google Scholar]
  13. Latchman D. S. Cell-type-specific splicing factors and the regulation of alternative RNA splicing. New Biol. 1990 Apr;2(4):297–303. [PubMed] [Google Scholar]
  14. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  15. Maldarelli F., Martin M. A., Strebel K. Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. J Virol. 1991 Nov;65(11):5732–5743. doi: 10.1128/jvi.65.11.5732-5743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Malim M. H., McCarn D. F., Tiley L. S., Cullen B. R. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. J Virol. 1991 Aug;65(8):4248–4254. doi: 10.1128/jvi.65.8.4248-4254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Page K. A., Landau N. R., Littman D. R. Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol. 1990 Nov;64(11):5270–5276. doi: 10.1128/jvi.64.11.5270-5276.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pomerantz R. J., Seshamma T., Trono D. Efficient replication of human immunodeficiency virus type 1 requires a threshold level of Rev: potential implications for latency. J Virol. 1992 Mar;66(3):1809–1813. doi: 10.1128/jvi.66.3.1809-1813.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  23. Rosen C. A., Pavlakis G. N. Tat and Rev: positive regulators of HIV gene expression. AIDS. 1990 Jun;4(6):499–509. [PubMed] [Google Scholar]
  24. Rosen C. A., Terwilliger E., Dayton A., Sodroski J. G., Haseltine W. A. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071–2075. doi: 10.1073/pnas.85.7.2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schwartz S., Felber B. K., Pavlakis G. N. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol. 1992 Jan;66(1):150–159. doi: 10.1128/jvi.66.1.150-159.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Trono D., Andino R., Baltimore D. An RNA sequence of hundreds of nucleotides at the 5' end of poliovirus RNA is involved in allowing viral protein synthesis. J Virol. 1988 Jul;62(7):2291–2299. doi: 10.1128/jvi.62.7.2291-2299.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Trono D., Baltimore D. A human cell factor is essential for HIV-1 Rev action. EMBO J. 1990 Dec;9(12):4155–4160. doi: 10.1002/j.1460-2075.1990.tb07638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Trono D., Feinberg M. B., Baltimore D. HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus. Cell. 1989 Oct 6;59(1):113–120. doi: 10.1016/0092-8674(89)90874-x. [DOI] [PubMed] [Google Scholar]
  29. Trono D. Partial reverse transcripts in virions from human immunodeficiency and murine leukemia viruses. J Virol. 1992 Aug;66(8):4893–4900. doi: 10.1128/jvi.66.8.4893-4900.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vaishnav Y. N., Vaishnav M., Wong-Staal F. Identification and characterization of a nuclear factor that specifically binds to the Rev response element (RRE) of human immunodeficiency virus type 1 (HIV-1). New Biol. 1991 Feb;3(2):142–150. [PubMed] [Google Scholar]

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