Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Dec;83(24):9734–9738. doi: 10.1073/pnas.83.24.9734

Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus.

B M Peterlin, P A Luciw, P J Barr, M D Walker
PMCID: PMC387215  PMID: 3025848

Abstract

The genome of human immunodeficiency virus encodes a protein that dramatically elevates amounts of viral proteins. The precise mechanism of this trans-activation remains to be established. It has been reported that trans-activation can occur without major changes in the levels of mRNA. We constructed recombinant plasmids containing those viral sequences required in cis for trans-activation linked to the chloramphenicol acetyltransferase gene. These plasmids were introduced into cultured cells in either the presence or absence of a second plasmid that directed expression of the viral trans-activator protein. Expression of the chloramphenicol acetyltransferase gene was measured at the level of protein (by enzymatic assay) and RNA (by ribonuclease protection and primer extension). Our results demonstrate that trans-activation is accompanied by large increases in mRNA levels; these increases may be sufficient to explain the elevated levels of trans-activated protein.

Full text

PDF
9734

Images in this article

9737Image
on p.9737
9737Image
on p.9737
9737Image
on p.9737
9737Image
on p.9737
9737Image
on p.9737
9737Image
on p.9737
9738Image
on p.9738
9738Image
on p.9738

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan J. S., Coligan J. E., Lee T. H., McLane M. F., Kanki P. J., Groopman J. E., Essex M. A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients. Science. 1985 Nov 15;230(4727):810–813. doi: 10.1126/science.2997921. [DOI] [PubMed] [Google Scholar]
  2. Arya S. K., Gallo R. C. Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2209–2213. doi: 10.1073/pnas.83.7.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arya S. K., Guo C., Josephs S. F., Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. doi: 10.1126/science.2990040. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Dayton A. I., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986 Mar 28;44(6):941–947. doi: 10.1016/0092-8674(86)90017-6. [DOI] [PubMed] [Google Scholar]
  6. Derse D., Caradonna S. J., Casey J. W. Bovine leukemia virus long terminal repeat: a cell type-specific promoter. Science. 1985 Jan 18;227(4684):317–320. doi: 10.1126/science.2981431. [DOI] [PubMed] [Google Scholar]
  7. Fisher A. G., Feinberg M. B., Josephs S. F., Harper M. E., Marselle L. M., Reyes G., Gonda M. A., Aldovini A., Debouk C., Gallo R. C. The trans-activator gene of HTLV-III is essential for virus replication. 1986 Mar 27-Apr 2Nature. 320(6060):367–371. doi: 10.1038/320367a0. [DOI] [PubMed] [Google Scholar]
  8. Fisher A. G., Ratner L., Mitsuya H., Marselle L. M., Harper M. E., Broder S., Gallo R. C., Wong-Staal F. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects. Science. 1986 Aug 8;233(4764):655–659. doi: 10.1126/science.3014663. [DOI] [PubMed] [Google Scholar]
  9. Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  11. Gazdar A. F., Carney D. N., Bunn P. A., Russell E. K., Jaffe E. S., Schechter G. P., Guccion J. G. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980 Mar;55(3):409–417. [PubMed] [Google Scholar]
  12. Gluckman J. C., Klatzmann D., Montagnier L. Lymphadenopathy-associated-virus infection and acquired immunodeficiency syndrome. Annu Rev Immunol. 1986;4:97–117. doi: 10.1146/annurev.iy.04.040186.000525. [DOI] [PubMed] [Google Scholar]
  13. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  16. Haase A. T. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
  17. Hess J. L., Clements J. E., Narayan O. cis- and trans-acting transcriptional regulation of visna virus. Science. 1985 Aug 2;229(4712):482–485. doi: 10.1126/science.2990051. [DOI] [PubMed] [Google Scholar]
  18. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  19. Kan N. C., Franchini G., Wong-Staal F., DuBois G. C., Robey W. G., Lautenberger J. A., Papas T. S. Identification of HTLV-III/LAV sor gene product and detection of antibodies in human sera. Science. 1986 Mar 28;231(4745):1553–1555. doi: 10.1126/science.3006245. [DOI] [PubMed] [Google Scholar]
  20. Khoury G., Gruss P. Enhancer elements. Cell. 1983 Jun;33(2):313–314. doi: 10.1016/0092-8674(83)90410-5. [DOI] [PubMed] [Google Scholar]
  21. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  22. Klemenz R., Hultmark D., Gehring W. J. Selective translation of heat shock mRNA in Drosophila melanogaster depends on sequence information in the leader. EMBO J. 1985 Aug;4(8):2053–2060. doi: 10.1002/j.1460-2075.1985.tb03891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Krieg P. A., Melton D. A. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res. 1984 Sep 25;12(18):7057–7070. doi: 10.1093/nar/12.18.7057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lane H. C., Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol. 1985;3:477–500. doi: 10.1146/annurev.iy.03.040185.002401. [DOI] [PubMed] [Google Scholar]
  25. Lee T. H., Coligan J. E., Allan J. S., McLane M. F., Groopman J. E., Essex M. A new HTLV-III/LAV protein encoded by a gene found in cytopathic retroviruses. Science. 1986 Mar 28;231(4745):1546–1549. doi: 10.1126/science.3006243. [DOI] [PubMed] [Google Scholar]
  26. Levy J. A., Cheng-Mayer C., Dina D., Luciw P. A. AIDS retrovirus (ARV-2) clone replicates in transfected human and animal fibroblasts. Science. 1986 May 23;232(4753):998–1001. doi: 10.1126/science.3010461. [DOI] [PubMed] [Google Scholar]
  27. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
  28. Levy J. A., Kaminsky L. S., Morrow W. J., Steimer K., Luciw P., Dina D., Hoxie J., Oshiro L. Infection by the retrovirus associated with the acquired immunodeficiency syndrome. Clinical, biological, and molecular features. Ann Intern Med. 1985 Nov;103(5):694–699. doi: 10.7326/0003-4819-103-5-694. [DOI] [PubMed] [Google Scholar]
  29. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–1191. doi: 10.1146/annurev.bi.55.070186.005443. [DOI] [PubMed] [Google Scholar]
  30. Luciw P. A., Potter S. J., Steimer K., Dina D., Levy J. A. Molecular cloning of AIDS-associated retrovirus. Nature. 1984 Dec 20;312(5996):760–763. doi: 10.1038/312760a0. [DOI] [PubMed] [Google Scholar]
  31. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
  32. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature. 1986 Feb 13;319(6054):555–559. doi: 10.1038/319555a0. [DOI] [PubMed] [Google Scholar]
  33. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  34. Sanchez-Pescador R., Power M. D., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., Renard A., Randolph A., Levy J. A. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484–492. doi: 10.1126/science.2578227. [DOI] [PubMed] [Google Scholar]
  35. Santerre R. F., Cook R. A., Crisel R. M., Sharp J. D., Schmidt R. J., Williams D. C., Wilson C. P. Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic beta cells. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4339–4343. doi: 10.1073/pnas.78.7.4339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Seigel L. J., Ratner L., Josephs S. F., Derse D., Feinberg M. B., Reyes G. R., O'Brien S. J., Wong-Staal F. Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity. Virology. 1986 Jan 15;148(1):226–231. doi: 10.1016/0042-6822(86)90419-8. [DOI] [PubMed] [Google Scholar]
  37. Slamon D. J., Shimotohno K., Cline M. J., Golde D. W., Chen I. S. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. doi: 10.1126/science.6089351. [DOI] [PubMed] [Google Scholar]
  38. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  39. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  40. Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
  41. Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. doi: 10.1126/science.2990041. [DOI] [PubMed] [Google Scholar]
  42. Sodroski J., Rosen C., Wong-Staal F., Salahuddin S. Z., Popovic M., Arya S., Gallo R. C., Haseltine W. A. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985 Jan 11;227(4683):171–173. doi: 10.1126/science.2981427. [DOI] [PubMed] [Google Scholar]
  43. Sompayrac L. M., Danna K. J. Efficient infection of monkey cells with DNA of simian virus 40. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7575–7578. doi: 10.1073/pnas.78.12.7575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Suggs S. V., Wallace R. B., Hirose T., Kawashima E. H., Itakura K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6613–6617. doi: 10.1073/pnas.78.11.6613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  46. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  47. Wong-Staal F., Gallo R. C. Human T-lymphotropic retroviruses. Nature. 1985 Oct 3;317(6036):395–403. doi: 10.1038/317395a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy