Repression of Human T-Cell Leukemia Virus Type 1 and Type 2 Replication by a Viral mRNA-Encoded Posttranscriptional Regulator

Younis, Ihab; Khair, Lyne; Dundr, Miroslav; Lairmore, Michael Dale; Franchini, Genoveffa; Green, Patrick L.

doi:10.1128/jvi.78.20.11077-11083.2004

Cited by 73 publications

(109 citation statements)

References 49 publications

(38 reference statements)

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…Like HTLV-1, Gag, Env, Tax, Rex, and truncated Rex of HTLV-2 can be detected consistently by western blot in infected cell lines (data not shown). p28 has functional analogy with HTLV-1 p30 and to date, p28 like p30, has not been detected in HTLV infected cells by western blot (Younis et al, 2004). Indeed, by real-time PCR, p30 mRNA levels were low, which is consistent with the failure to detect p30 protein.…”

Section: Discussionmentioning

confidence: 79%

“…ML765, ML627, and ML766, used to quantify env transcripts are specific for HTLV-1 exon 1/exon 2 (terminal exon for env) junctions utilizing splice acceptor sites at nt 4501, nt 4641, and nt 4658, respectively and ML628, ML764, and ML760, specific for HTLV-1 p13, HBZ minor spliced transcript, and gag/pol unspliced transcript, respectively, were generated by PCR amplification followed by insertion into pCRScript (Stratagene, La Jolla, CA): ML765, partial exon 1 (nt 103-119) fused to exon 2 (nt 4501-4831) and partial intron 2 (nt 4832-4919); ML627, partial exon 1 (nt 100-119) fused to exon 2 (nt 4641-4831) and partial intron 2 (nt 4832-4919); ML766, partial exon 1 (nt 103-119) fused to exon 2 (nt 4658-4831) and partial intron 2 (nt 4832-4919); ML628, partial exon 1 (nt 102-119) fused to partial exon 3 (nt 6875-7170); ML764 (numbering is based on ACH antisense strand proviral sequence beginning with the last nt of U5 of the 3′ LTR), exon 1 (nt 212-225) fused to partial exon 2 (nt 1765-1826); ML760, nt 920-1049. IY531, and IY595 (Younis et al, 2004) were used to quantify HTLV-2 tax/rex and env mRNAs, respectively. ML637, ML638, ML674 and ML761, specific for HTLV-2 p28, p22/p20rex-1, p28, p22/p20rex-2, p10/p11 and gag/pol transcripts, respectively were generated by PCR amplification of fragments across the appropriate splice junction followed by insertion into pCRScript (Stratagene, La Jolla, CA): ML637, partial exon 1 (nt 117-135) fused to partial terminal exon (nt 6630-6984); ML638, partial exon 1 (nt 117-135) fused to partial exon 3 (nt 6900-6984); ML674, partial exon 1 (nt 123-135) fused to exon 2 (nt 4730-4869) fused to partial terminal exon (nt 6493-6508); ML675, partial exon 1 (nt 123-135) fused to exon 2 (nt 4730-4869) fused to partial terminal exon (nt 6630-6645); ML761, nt 1887-1986. pBluescripthGAPDH was a gift from K. Boris-Lawrie (Ohio State University, Columbus, OH).…”

Section: Plasmidsmentioning

confidence: 99%

“…p30, expressed from a doubly-spliced mRNA, is a multifunctional regulator that differentially modulates viral and/or cellular gene expression at the transcriptional level through association with cellular proteins including p300/CBP and TIP60 (Awasthi et al, 2005;Zhang et al, 2001;Zhang et al, 2000) and post-transcriptionally via binding and retaining tax/rex mRNA in the nucleus (Nicot et al, 2004;Younis et al, 2006;Younis et al, 2004). Although p30 is dispensable in vitro for replication and cellular transformation (Derse et al, 1997;Robek et al, 1998), it is required to promote virus survival and persistence in infected animals (Silverman et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…HTLV-2 p28, with the potential to be expressed from two distinct singly-spliced mRNAs (both of these mRNAs also have the potential to produce p22/ p20rex), is at least in part functionally homologous to HTLV-1 p30. It functions to repress viral replication post-transcriptionally by retaining tax/rex mRNA in the nucleus (Younis et al, 2004). p10 and p11 are expressed from the same doubly spliced mRNA in separate but overlapping reading frames.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Green

2007

Journal of Virological Methods

Self Cite

View full text Add to dashboard Cite

SummaryHTLV-1 and HTLV-2 are highly related delta-retroviruses that infect and transform T-lymphocytes, but have distinct pathogenic properties. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the comparative levels of all known HTLV-1 and HTLV-2 viral mRNAs in different transformed cell lines and at different stages of virus infection have not been assessed. In this study, we compiled a series of oligonucleotide primer pairs and probes to quantify both HTLV-1 and HTLV-2 mRNA species using real-time RT-PCR. The optimized reaction for detection of each mRNA had amplification efficiency greater than 90% with a linear range spanning 25 to 2.5 × 10 7 copies. The R 2 s of all standard curves were greater than 0.97. Quantitation of HTLV mRNAs between different cell lines showed variability (gag/pol ≥ tax/rex > env ≥ accessory proteins), but the overall levels of each mRNA relative to each other within a cell line were similar. These results provide a method to quantify all specific mRNAs from both HTLV-1 and HTLV-2, which can be used to evaluate further viral gene expression and correlate transcript levels to key stages of the virus life cycle and ultimately, pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 79%

Section: Plasmidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Green

2007

Journal of Virological Methods

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to Tax, HTLV-1 and HTLV-2 genomes also encode the p30 and p28 proteins, respectively (Nicot et al, 2004;Younis et al, 2004). Each of these two proteins has been shown to retain the doubly spliced mRNA encoding the Tax and Rex proteins in the nucleus.…”

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

View full text Add to dashboard Cite

Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human Tcell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-jB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.

show abstract

Thioredoxin reductase gene expression and activity among human T‐cell lymphotropic virus type 1–infected patients

Yaghoubi

Youssefi

Hashemy

et al. 2018

Journal of Medical Virology

View full text Add to dashboard Cite

Background The thioredoxin (Trx) system is a reducing complex, consisting of Trx, Trx reductase (TrxR), and NADPH, that scavenges reactive oxygen species. The system is a natural protective mechanism to prevent apoptosis and progression of oxidative stress‐related diseases. The present study was conducted to explore possible changes in TrxR activity and gene expression as a response to the oxidative stress during HTLV‐1 infection. Materials and Methods Blood samples were collected from 40 HTLV‐1‐infected patients and 40 age‐ and sex‐matched healthy controls. The patient group consisted of chronic asymptomatic carriers and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM‐TSP) patients. A commercial kit was used to measure the TrxR enzyme activity, and real‐time polymerase chain reaction was performed to evaluate TrxR gene expression in extracted peripheral blood mononuclear cells (PBMCs). Results A decreasing pattern of TrxR enzyme activity was observed among control, carrier, and HAM‐TSP groups (mean ± SD; controls, 0.1734 ± 0.056; carriers, 0.134 ± 0.065; and HAM‐TSP, 0.0928 ± 0.047 µmol/min/mL). Cellular TrxR gene expression showed the same decreasing trend. The fold differences of gene expression in carriers and HAM‐TSP groups compared with healthy controls were 0.8 and 0.7 vs 1, respectively. Conclusion We found a reduction in TrxR expression as well as serum enzyme activity in HTLV‐1‐infected individuals, particularly in HAM‐TSP patients. The reduced TrxR activity during HTLV‐1 infection may hamper the natural protective mechanisms, thereby contributes to virus‐induced complications.

show abstract

Repression of Human T-Cell Leukemia Virus Type 1 and Type 2 Replication by a Viral mRNA-Encoded Posttranscriptional Regulator

Cited by 73 publications

References 49 publications

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

Thioredoxin reductase gene expression and activity among human T‐cell lymphotropic virus type 1–infected patients

Contact Info

Product

Resources

About