Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compared to other T-lymphotropic human retroviruses, human T-cell leukemia (lymphotropic) virus I (HTLV-I) and HTLV-II, the acquired immunodeficiency syndrome (AIDS)-associated virus, HTLV-III, is a nontransforming cytopathic virus without immortalizing activity. Thus the virus replication is an important event in the manifestation of this disease, and the interruption of viral replication offers an important strategy for the control of AIDS. For this reason we have purified the reverse transcriptase (RT) from HTLV-III and from HTLV-III infected cells to study the structure-activity relationship of RT inhibitors developed in our laboratory. The cellular DNA polymerases from H9 cells were also purified to study the selectivity of RT inhibitors. Purified HTLV-III RT has several distinguishing features: (a) unlike the HTLV-I enzyme it is highly stable and can be kept for several weeks without any loss of activity; (b) using identical procedures of isolation the HTLV-III enzyme shows a much higher activity than does the enzyme from HTLV-I; (c) the Vmax for HTLV-III RT is by severalfold higher than that for the HTLV-I enzyme in the presence of (rC)n X (dG)12 and (rCm)n X (dG)12, and besides the usual template-primers used for RT assay this enzyme has a relatively high affinity for (rAm)n X (dT)12; and (d) the cationic requirements for the transcription of various template-primers are unusual. The purified enzyme has a molecular weight of 95,000-98,000, as judged by the gel filtration method. The purified HTLV-III RT was inhibited by a partially thiolated polycytidylic acid (5-mercaptopolycytidylic acid); the cellular DNA polymerase beta from H9 cells was not sensitive to 5-mercaptopolycytidylic acid. Germanin (synonym, suramin), an antiprotozoan drug, also inhibits HTLV-III RT activity, but the DNA polymerase alpha activity was also sensitive to Germanin. The nonspecific effect of Germanin is probably due to the high content of sulfonic acid residues. This paper describes new approaches for designing specific inhibitors of retroviral reverse transcriptases which may be useful in developing a potential drug against AIDS.
 ...
PMID:Inhibitors of retroviral DNA polymerase: their implication in the treatment of AIDS. 241 Jan 12

Polymerase chain reaction (PCR) involves alternate denaturing and re-annealing of DNA in test samples in the presence of appropriate oligonucleotide primers complementary to opposite strands of the target DNA together with a heat-stable DNA polymerase, Mg2+ and the four nucleotide triphosphates. DNA target segments can be 'amplified' ten-millionfold by 25-35 such cycles. Even greater amplification (approximately 10(12)-fold) with enhanced specificity can be obtained by a second set of amplification cycles using a further pair of 'nested' primers sited within the DNA sequence defined by the original primers. PCR can be applied to the study of the whole range of transfusion-transmitted infections, both plasma and cell associated; RNA viruses can be analyzed if a DNA copy is made from the viral RNA by treatment with reverse transcriptase. In a transfusion context, the retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II), HCV and HBV have been the viruses most intensively subjected to PCR analysis. The advantages of PCR in this context include its ability to detect virus during the 'window period' or seronegative stages of infections and its value as a marker for viraemia and for the detection of viruses in products made from large pools of plasma. True immunity may also be differentiated from persistent infection in the presence of antibody. Similarly, PCR can overcome problems of diagnosis of acute infection caused by the presence of passively transferred antibody. Detailed strain differentiation is also possible by PCR, in conjunction with sequencing or with the aid of restriction endonucleases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Polymerase chain reaction and transfusion microbiology. 838 93

By immunoprecipitation analysis, enhanced p53 expression was detected in 3 of 4 adult T-cell leukemia (ATL) cell lines, 1 of 3 HTLV-I-infected cell lines and 1 of 5 fresh ATL samples, compared with phytohemagglutinin-stimulated peripheral blood lymphocytes. Among these 5 high expressers, p53 missense mutations were indicated in 2 ATL cell lines and 1 fresh ATL sample by extensive p53 cDNA and genomic DNA polymerase chain reaction single-strand conformation polymorphism analysis. No mutation was found throughout the entire coding region of the remaining 2 high expressers (1 ATL and 1 HTLV-I-infected cell lines) and low expressers of p53 (2 HTLV-I-infected cell lines). Tax oncoprotein expression was found in these 2 high p53 expressers in which p53 mutation was not present, but not in low p53 expressers or cells carrying this mutation. The levels of p53 mRNA were similar among the samples regardless of p53 levels. Posttranscriptional mechanisms other than missense mutation would thus appear to increase p53 in the Tax-expressing cells but not in cells containing undetectable levels of Tax. No complex formation between p53 and Tax was observed.
 ...
PMID:Aberrant expression of the p53 tumor suppressor gene in adult T-cell leukemia and HTLV-I-infected cells. 844 26