Abstract
We analyzed the equine infectious anemia virus (EIAV) long terminal repeat (LTR) for sequences that influence its promoter activity and ability to be trans-activated by the EIAV tat gene product. A series of LTR deletion mutants and recombinants between LTR and simian virus 40 (SV40) regulatory sequences were used for these studies. We were able to identify the EIAV promoter region and showed that sequences within the U3 region significantly inhibited LTR-directed transcription. However, when placed in a heterologous context (SV40 promoter) these U3 sequences functioned as an enhancer. trans-activation of the EIAV LTR was found to depend upon sequences downstream of the transcription initiation site and also within U3. Deletion mutagenesis experiments showed that the major downstream element was present in a 46-nucleotide stretch (+4 to +50). An SV40 promoter construct containing these sequences could be trans-activated in cells expressing the EIAV tat gene product. For comparative purposes we also examined the LTR of another animal lentivirus, caprine arthritis-encephalitis virus (CAEV), for positive and negative transcriptional regulatory elements and demonstrated the presence of an enhancer within its U3 sequence. There is evidence that trans-activation of the CAEV LTR requires U3 sequences. When the EIAV U3 region was replaced by the CAEV U3 sequence, the promoter activity of the EIAV LTR was markedly elevated, but the responsiveness to the EIAV trans-activator could not be restored.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arya S. K., Beaver B., Jagodzinski L., Ensoli B., Kanki P. J., Albert J., Fenyo E. M., Biberfeld G., Zagury J. F., Laure F. New human and simian HIV-related retroviruses possess functional transactivator (tat) gene. Nature. 1987 Aug 6;328(6130):548–550. doi: 10.1038/328548a0. [DOI] [PubMed] [Google Scholar]
- Arya S. K., Gallo R. C. Human immunodeficiency virus type 2 long terminal repeat: analysis of regulatory elements. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9753–9757. doi: 10.1073/pnas.85.24.9753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dahlberg J. E., Gaskin J. M., Perk K. Morphological and immunological comparison of caprine arthritis encephalitis and ovine progressive pneumonia viruses. J Virol. 1981 Sep;39(3):914–919. doi: 10.1128/jvi.39.3.914-919.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis J. L., Clements J. E. Characterization of a cDNA clone encoding the visna virus transactivating protein. Proc Natl Acad Sci U S A. 1989 Jan;86(2):414–418. doi: 10.1073/pnas.86.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Derse D., Dorn P. L., Levy L., Stephens R. M., Rice N. R., Casey J. W. Characterization of equine infectious anemia virus long terminal repeat. J Virol. 1987 Mar;61(3):743–747. doi: 10.1128/jvi.61.3.743-747.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorn P. L., Derse D. cis- and trans-acting regulation of gene expression of equine infectious anemia virus. J Virol. 1988 Sep;62(9):3522–3526. doi: 10.1128/jvi.62.9.3522-3526.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emerman M., Guyader M., Montagnier L., Baltimore D., Muesing M. A. The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1. EMBO J. 1987 Dec 1;6(12):3755–3760. doi: 10.1002/j.1460-2075.1987.tb02710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feng S., Holland E. C. HIV-1 tat trans-activation requires the loop sequence within tar. Nature. 1988 Jul 14;334(6178):165–167. doi: 10.1038/334165a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Guyader M., Emerman M., Sonigo P., Clavel F., Montagnier L., Alizon M. Genome organization and transactivation of the human immunodeficiency virus type 2. Nature. 1987 Apr 16;326(6114):662–669. doi: 10.1038/326662a0. [DOI] [PubMed] [Google Scholar]
- Hauber J., Cullen B. R. Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat. J Virol. 1988 Mar;62(3):673–679. doi: 10.1128/jvi.62.3.673-679.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hauber J., Perkins A., Heimer E. P., Cullen B. R. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6364–6368. doi: 10.1073/pnas.84.18.6364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hess J. L., Pyper J. M., Clements J. E. Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat. J Virol. 1986 Nov;60(2):385–393. doi: 10.1128/jvi.60.2.385-393.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hess J. L., Small J. A., Clements J. E. Sequences in the visna virus long terminal repeat that control transcriptional activity and respond to viral trans-activation: involvement of AP-1 sites in basal activity and trans-activation. J Virol. 1989 Jul;63(7):3001–3015. doi: 10.1128/jvi.63.7.3001-3015.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakobovits A., Smith D. H., Jakobovits E. B., Capon D. J. A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator. Mol Cell Biol. 1988 Jun;8(6):2555–2561. doi: 10.1128/mcb.8.6.2555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawakami T., Sherman L., Dahlberg J., Gazit A., Yaniv A., Tronick S. R., Aaronson S. A. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology. 1987 Jun;158(2):300–312. doi: 10.1016/0042-6822(87)90202-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Okamoto T., Wong-Staal F. Demonstration of virus-specific transcriptional activator(s) in cells infected with HTLV-III by an in vitro cell-free system. Cell. 1986 Oct 10;47(1):29–35. doi: 10.1016/0092-8674(86)90363-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Rushlow K., Olsen K., Stiegler G., Payne S. L., Montelaro R. C., Issel C. J. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus. Virology. 1986 Dec;155(2):309–321. doi: 10.1016/0042-6822(86)90195-9. [DOI] [PubMed] [Google Scholar]
- Sherman L., Gazit A., Yaniv A., Dahlberg J. E., Tronick S. R. Nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus. Virus Res. 1986 Aug;5(2-3):145–155. doi: 10.1016/0168-1702(86)90014-6. [DOI] [PubMed] [Google Scholar]
- Sherman L., Gazit A., Yaniv A., Kawakami T., Dahlberg J. E., Tronick S. R. Localization of sequences responsible for trans-activation of the equine infectious anemia virus long terminal repeat. J Virol. 1988 Jan;62(1):120–126. doi: 10.1128/jvi.62.1.120-126.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Viglianti G. A., Mullins J. I. Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1. J Virol. 1988 Dec;62(12):4523–4532. doi: 10.1128/jvi.62.12.4523-4532.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yaniv A., Dahlberg J. E., Tronick S. R., Chiu I. M., Aaronson S. A. Molecular cloning of integrated caprine arthritis-encephalitis virus. Virology. 1985 Sep;145(2):340–345. doi: 10.1016/0042-6822(85)90169-2. [DOI] [PubMed] [Google Scholar]
- Yaniv A., Dahlberg J., Gazit A., Sherman L., Chiu I. M., Tronick S. R., Aaronson S. A. Molecular cloning and physical characterization of integrated equine infectious anemia virus: molecular and immunologic evidence of its close relationship to ovine and caprine lentiviruses. Virology. 1986 Oct 15;154(1):1–8. doi: 10.1016/0042-6822(86)90424-1. [DOI] [PubMed] [Google Scholar]
