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J Virol. Aug 1992; 66(8): 4769–4777.
PMCID: PMC241304

Activation of bovine leukemia virus transcription in lymphocytes from infected sheep: rapid transition through early to late gene expression.

Abstract

Bovine leukemia virus (BLV) expression is mostly silent in peripheral blood mononuclear cells (PBMCs) of infected animals. However, when infected cells are cultured, they are stimulated to produce virus. We studied viral transcription in PBMCs taken from BLV-infected sheep because the pattern of transcriptional activation in these cells should closely mimic activation of virus expression within mononuclear cells in vivo. BLV transcription was activated as early as 30 min after PBMCs were cultured. Expression was characterized by early and late stages, each distinguished by a unique pattern of cytoplasmic RNAs. In early expression, cytoplasmic viral RNA was exclusively the doubly spliced tax/rex transcript, although all transcripts were present in the nucleus. Early expression gave way rapidly to late expression, in which all viral transcripts accumulated in the cytoplasm. The polyclonal B-cell activator lipopolysaccharide increased the amount of viral RNA by at least twofold but did not alter the pattern of transcription. The transition from early to late expression required new protein synthesis and was blocked by the inhibitor cycloheximide. This requirement reflects the essential role of the viral Rex protein in the transition, but synthesis of cellular factors may be required as well. These results provide the first demonstration of staged viral expression in lymphocytes naturally infected by either BLV or the closely related human T-cell leukemia virus (HTLV) and validate the model of BLV and HTLV gene expression that previously was derived from transfection experiments performed mainly in nonlymphoid cells.

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  • Arrigo SJ, Chen IS. 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. [PubMed]
  • Aviv H, Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. [PMC free article] [PubMed]
  • Burny A, Cleuter Y, Kettmann R, Mammerickx M, Marbaix G, Portetelle D, van den Broeke A, Willems L, Thomas R. Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer. Vet Microbiol. 1988 Jul;17(3):197–218. [PubMed]
  • Chatterjee R, Gupta P, Kashmiri SV, Ferrer JF. Phytohemagglutinin activation of the transcription of the bovine leukemia virus genome requires de novo protein synthesis. J Virol. 1985 Jun;54(3):860–863. [PMC free article] [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Cochrane AW, Chen CH, Rosen CA. Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1198–1202. [PMC free article] [PubMed]
  • Derse D. Bovine leukemia virus transcription is controlled by a virus-encoded trans-acting factor and by cis-acting response elements. J Virol. 1987 Aug;61(8):2462–2471. [PMC free article] [PubMed]
  • Derse D. trans-acting regulation of bovine leukemia virus mRNA processing. J Virol. 1988 Apr;62(4):1115–1119. [PMC free article] [PubMed]
  • Emerman M, Vazeux R, Peden K. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 1989 Jun 30;57(7):1155–1165. [PubMed]
  • Felber BK, Derse D, Athanassopoulos A, Campbell M, Pavlakis GN. Cross-activation of the Rex proteins of HTLV-I and BLV and of the Rev protein of HIV-1 and nonreciprocal interactions with their RNA responsive elements. New Biol. 1989 Dec;1(3):318–328. [PubMed]
  • Ferrer JF, Gupta P. Notification to readers. Expression of bovine leukemia virus genome is blocked by a nonimmunoglobulin protein in plasma from infected cattle. Science. 1989 May 12;244(4905):632–632. [PubMed]
  • Gessain A, Louie A, Gout O, Gallo RC, Franchini G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy. J Virol. 1991 Mar;65(3):1628–1633. [PMC free article] [PubMed]
  • Hadzopoulou-Cladaras M, Felber BK, Cladaras C, Athanassopoulos A, Tse A, Pavlakis GN. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region. J Virol. 1989 Mar;63(3):1265–1274. [PMC free article] [PubMed]
  • Hammarskjöld ML, Heimer J, Hammarskjöld B, Sangwan I, Albert L, Rekosh D. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 1989 May;63(5):1959–1966. [PMC free article] [PubMed]
  • Heaphy S, Dingwall C, Ernberg I, Gait MJ, Green SM, Karn J, Lowe AD, Singh M, Skinner MA. 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. [PubMed]
  • Herschman HR. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. [PubMed]
  • Hidaka M, Inoue J, Yoshida M, Seiki M. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J. 1988 Feb;7(2):519–523. [PMC free article] [PubMed]
  • Inoue J, Yoshida M, Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. [PMC free article] [PubMed]
  • Jeang KT, Boros I, Brady J, Radonovich M, Khoury G. Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol. 1988 Dec;62(12):4499–4509. [PMC free article] [PubMed]
  • Jensen WA, Rovnak J, Cockerell GL. In vivo transcription of the bovine leukemia virus tax/rex region in normal and neoplastic lymphocytes of cattle and sheep. J Virol. 1991 May;65(5):2484–2490. [PMC free article] [PubMed]
  • Kettmann R, Marbaix G, Cleuter Y, Portetelle D, Mammerickx M, Burny A. Genomic integration of bovine leukemia provirus and lack of viral RNA expression in the target cells of cattle with different responses to BLV infection. Leuk Res. 1980;4(6):509–519. [PubMed]
  • Kim SY, 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. [PMC free article] [PubMed]
  • Kinoshita T, Shimoyama M, Tobinai K, Ito M, Ito S, Ikeda S, Tajima K, Shimotohno K, Sugimura T. Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5620–5624. [PMC free article] [PubMed]
  • Klotman ME, Kim S, Buchbinder A, DeRossi A, Baltimore D, Wong-Staal F. Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5011–5015. [PMC free article] [PubMed]
  • Lagarias DM, Radke K. Transcriptional activation of bovine leukemia virus in blood cells from experimentally infected, asymptomatic sheep with latent infections. J Virol. 1989 May;63(5):2099–2107. [PMC free article] [PubMed]
  • Lagarias DM, Radke K. Transient increases of blood mononuclear cells that could express bovine leukemia virus early after experimental infection of sheep. Microb Pathog. 1990 Sep;9(3):147–158. [PubMed]
  • Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. [PubMed]
  • Malim MH, Tiley LS, McCarn DF, Rusche JR, Hauber J, Cullen BR. 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. [PubMed]
  • Michael NL, Morrow P, Mosca J, Vahey M, Burke DS, Redfield RR. Induction of human immunodeficiency virus type 1 expression in chronically infected cells is associated primarily with a shift in RNA splicing patterns. J Virol. 1991 Mar;65(3):1291–1303. [PMC free article] [PubMed]
  • Ohta M, Nyunoya H, Tanaka H, Okamoto T, Akagi T, Shimotohno K. Identification of a cis-regulatory element involved in accumulation of human T-cell leukemia virus type II genomic mRNA. J Virol. 1988 Dec;62(12):4445–4451. [PMC free article] [PubMed]
  • Pomerantz RJ, Trono D, Feinberg MB, 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. [PubMed]
  • Powers MA, Grossman D, Kidd LC, Radke K. Episodic occurrence of antibodies against the bovine leukemia virus Rex protein during the course of infection in sheep. J Virol. 1991 Sep;65(9):4959–4965. [PMC free article] [PubMed]
  • Seiki M, Inoue J, Takeda T, Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. [PMC free article] [PubMed]
  • Seiki M, Inoue J, Hidaka M, Yoshida M. Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7124–7128. [PMC free article] [PubMed]
  • Siomi H, Shida H, Nam SH, Nosaka T, Maki M, Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. [PubMed]
  • Slamon DJ, Press MF, Souza LM, Murdock DC, Cline MJ, Golde DW, Gasson JC, Chen IS. Studies of the putative transforming protein of the type I human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1427–1430. [PubMed]
  • Willems L, Gegonne A, Chen G, Burny A, Kettmann R, Ghysdael J. The bovine leukemia virus p34 is a transactivator protein. EMBO J. 1987 Nov;6(11):3385–3389. [PMC free article] [PubMed]

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