HTLV
            <i>x</i>
            -Gene Product: Requirement for the
            <i>env</i>
            Methionine Initiation Codon

Wachsman, William; Golde, David W.; Temple, Patricia A.; Orr, Elizabeth C.; Clark, Steven C.; Chen, Irvin S. Y.

doi:10.1126/science.2990032

Cited by 57 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RT-PCR performed on RNA extracted from the C1O/MJ cell line amplified a 381-base-pair (bp) DNA molecule ( Fig. 1) corresponding to the doubly spliced pX mRNA that has been described (23,24). In addition, other amplified DNA molecules were also shown after the gel was stained with ethidium bromide and after hybridization with the HTLV-I genomic pMT-2 probe (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The cDNAs obtained from the N1186 cell line had the same splicing pattern as the equivalent messages in the C1O/MJ cell line. pX mRNA corresponded to the doubly spliced message characterized in the past (23,24). It joins transcript from the 5' long terminal repeat (noncoding first exon up to nucleotide 471) to RNA from the downstream region ofpol (second exon: nucleotides 4993-5183), which is spliced to transcript from the pX region (third exon: from nucleotide 7302 on); this pX mRNA has a coding capacity for tax, rex, and p211x (26).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Berneman

Gartenhaus

Reitz

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

142

120

View full text Add to dashboard Cite

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inability of most previous studies to readily detect HTLV-I RNA in infected individuals. By using the reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cells from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced mRNAs were demonstrated (pXA17, pX-p21rex, and pX-orflI mRNAs, where orf = open reading frame). The same splice sites were shown in the messages from uncultured ATL cells and from the HTLV-I-producing C1O/MJ cell line. Alternatively spliced pX mRNAs have the potential to code for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p2l'rx (pX-p2lrx mRNA). Since alternative splicing of HTLV

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Berneman

Gartenhaus

Reitz

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

142

120

View full text Add to dashboard Cite

show abstract

“…The X region of these viruses is transcribed into subgenomic transcripts (XmRNA) by doublesplicing mechanisms (Seiki et al, 1985;Sagata et al, 1985 b;Wachsman et al, 1985 ;Rice et al, 1987). The XmRNA encodes at least two distinct polypeptides using overlapping ORFs (x-lor: XBL-I and x-sor: XBL-II) (Sagata et al, 1985 a;Nagasbima et al, 1987;Rice et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Cooperative Regulation of Bovine Leukaemia Virus Gene Expression by Two Overlapping Open Reading Frames in the XBL Region

Itohara

Tomiyama

Ushimi

et al. 1988

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYBovine leukaemia virus (BLV) induces syncytia in productively infected ovine and bovine monolayer cells. Expression of the env gene directly determines the syncytiumforming activity, since the expression of a cloned env gene directed by the simian virus 40 (SV40) early promoter efficiently induced syncytia in transfected ovine embryonic (OE) cells. However a BLV 10ng terminal repeat (LTR)-directed expression plasmid (pLTRenv) failed to induce syncytia in transfected OE cells, suggesting insufficient promoter activity of the LTR sequences. To assess the role of the XBL genes, which are located in the 3' distal region of the genome, in viral gene expression we constructed SV40 early promoter-directed expression plasmids. These contained open reading frames (ORFs) in the XBL region, and were examined for syncytium-inducing activity by cotransfection with pLTRenv. The results suggest that both XBL-I (the longest ORF: x-lor) and XBL-II (a shorter overlapping ORF: x-sot) are trans-acting genes which cooperatively activate LTR-directed viral gene expression.

show abstract

“…The deduced amino acid sequence of Tax provides no evidence for intrinsic protein kinase or phosphatase activity (Seiki et al, 1985;Wachsman et al, 1985), suggesting that IKKg-directed formation of Tax/IKK complexes is necessary but not sucient for persistent IKK activation. In this regard, recent studies indicate that members of the MAP3K protein kinase family mediate physiologic activation of IKK via phosphorylation of the MAP2K activation loops present in the IKKa and IKKb catalytic subunits (Zandi and Karin, 1999).…”

Section: Tax-responsive Eectors Of Ikkmentioning

confidence: 99%

Persistent activation of NF-κB by the Tax transforming protein of HTLV-1: hijacking cellular IκB kinases

1999

View full text Add to dashboard Cite

Biochemical coupling of transcription factor NF-kB to antigen and co-stimulatory receptors is required for the temporal control of T-cell proliferation. In contrast to its transitory activation during normal growth-signal transduction, NF-kB is constitutively deployed in T-cells transformed by the type 1 human T-cell leukemia virus (HTLV-1). This viral/host interaction is mediated by the HTLV-1-encoded Tax protein, which has potent oncogenic properties. As reviewed here, Tax activates NF-kB primarily via a pathway leading to the chronic phosphorylation and degradation of IkBa, a cytoplasmic inhibitor of NF-kB. To access this pathway, Tax associates stably with a cytokine-inducible IkB kinase (IKK), which contains both catalytic (IKKa and IKKb) and noncatalytic (IKKg) subunits. Unlike their transiently induced counterparts in cytokine-treated cells, Taxassociated forms of IKKa and IKKb are persistently activated in HTLV-1-infected T cells. Acquisition of the deregulated IKK phenotype is contingent on the presence of IKKg, which functions as a molecular adaptor in the assembly of pathologic Tax/IkB kinase complexes. These ®ndings highlight a key mechanistic role for IKK in the Tax/NF-kB signaling axis and de®ne new intracellular targets for the therapeutic control of HTLV-1-associated disease.

show abstract

HTLV x -Gene Product: Requirement for the env Methionine Initiation Codon

Cited by 57 publications

References 34 publications

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Cooperative Regulation of Bovine Leukaemia Virus Gene Expression by Two Overlapping Open Reading Frames in the XBL Region

Persistent activation of NF-κB by the Tax transforming protein of HTLV-1: hijacking cellular IκB kinases

Contact Info

Product

Resources

About