Proteolytic Processing of the Human T-cell Lymphotropic Virus 1 Reverse Transcriptase: Identification of the N-Terminal Cleavage Site by Mass Spectrometry

2001 ◽  
Vol 392 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Pinky G. Agbuya ◽  
Nicholas E. Sherman ◽  
Laura K. Moen
Keyword(s):  
Mass Spectrometry ◽  
T Cell ◽  
Reverse Transcriptase ◽  
Cleavage Site ◽  
Proteolytic Processing ◽  
Human T Cell

Transcriptional activation of hTERT through the NF-κB pathway in HTLV-I–transformed cells

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2523-2531 ◽  
Author(s):  
Uma Sinha-Datta ◽  
Izumi Horikawa ◽  
Eriko Michishita ◽  
Abhik Datta ◽  
Janitzia C. Sigler-Nicot ◽  
...  
Keyword(s):  
T Cell ◽  
Reverse Transcriptase ◽  
Telomere Length ◽  
Transcriptional Activation ◽  
Type I ◽  
T Cell Leukemia ◽  
Htert Promoter ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract In immortal cells, the existence of a mechanism for the maintenance of telomere length is critical. In most cases this is achieved by the reactivation of telomerase, a cellular reverse transcriptase that prevents telomere shortening. Here we report that the telomerase gene (hTERT) promoter is up-regulated during transmission of human T-cell lymphotropic virus type-I (HTLV-I) to primary T cells in vitro and in ex vivo adult T-cell leukemia/lymphoma (ATLL) samples, but not asymptomatic carriers. Although Tax impaired induction of human telomerase reverse transcriptase (hTERT) mRNA in response to mitogenic stimulation, transduction of Tax into primary lymphocytes was sufficient to activate and maintain telomerase expression and telomere length when cultured in the absence of any exogenous stimulation. Transient transfection assays revealed that Tax stimulates the hTERT promoter through the nuclear factor κB (NF-κB) pathway. Consistently, Tax mutants inactive for NF-κB activation could not activate the hTERT or sustain telomere length in transduced primary lymphocytes. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays suggested that an increased binding of c-Myc and Sp1 is involved in the NF-κB–mediated activation of the hTERT promoter. This study establishes the role of Tax in regulation of telomerase expression, which may cooperate with other functions of Tax to promote HTLV-I–associated adult T-cell leukemia.

scholarly journals Susceptibility of Human T Cell Leukemia Virus Type I to Nucleoside Reverse Transcriptase Inhibitors

2003 ◽  
Vol 188 (3) ◽  
pp. 424-427 ◽  
Author(s):  
Shawn A. Hill ◽  
Patricia A. Lloyd ◽  
Shannon McDonald ◽  
Jennifer Wykoff ◽  
David Derse
Keyword(s):  
T Cell ◽  
Reverse Transcriptase ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
Cell Leukemia ◽  
Reverse Transcriptase Inhibitors ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Phenotypic and Genotypic Comparisons of Human T-Cell Leukemia Virus Type 1 Reverse Transcriptases from Infected T-Cell Lines and Patient Samples

2007 ◽  
Vol 81 (9) ◽  
pp. 4422-4428 ◽  
Author(s):  
Michael S. Mitchell ◽  
Ellen T. Bodine ◽  
Shawn Hill ◽  
Gerald Princler ◽  
Patricia Lloyd ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Reverse Transcriptase ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Consensus Sequence ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT It is well established that cell-free infection with human T-cell leukemia virus type 1 (HTLV-1) is less efficient than that with other retroviruses, though the specific infectivities of only a limited number of HTLV-1 isolates have been quantified. Earlier work indicated that a postentry step in the infectious cycle accounted for the poor cell-free infectivity of HTLV-1. To determine whether variations in the pol gene sequence correlated with virus infectivity, we sequenced and phenotypically tested pol genes from a variety of HTLV-1 isolates derived from primary sources, transformed cell lines, and molecular clones. The pol genes and deduced amino acid sequences from 23 proviruses were sequenced and compared with 14 previously published sequences, revealing a limited number of amino acid variations among isolates. The variations appeared to be randomly dispersed among primary isolates and proviruses from cell lines and molecular clones. In addition, there was no correlation between reverse transcriptase sequence and the disease phenotype of the original source of the virus isolate. HTLV-1 pol gene fragments encoding reverse transcriptase were amplified from a variety of isolates and were subcloned into HTLV-1 vectors for both single-cycle infection and spreading-infection assays. Vectors carrying pol genes that matched the consensus sequence had the highest titers, and those with the largest number of variations from the consensus had the lowest titers. The molecular clone from CS-1 cells had four amino acid differences from the consensus sequence and yielded infectious titers that were approximately eight times lower than those of vectors encoding a consensus reverse transcriptase.

scholarly journals Micromethod for assaying reverse transcriptase of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.

1987 ◽  
Vol 25 (1) ◽  
pp. 97-99 ◽  
Author(s):  
T J Spira ◽  
L H Bozeman ◽  
R C Holman ◽  
D T Warfield ◽  
S K Phillips ◽  
...  
Keyword(s):  
T Cell ◽  
Reverse Transcriptase ◽  
Virus Type ◽  
Type Iii ◽  
Human T Cell
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