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1

HIV and human endogenous retroviruses: An hypothesis with therapeutic implications

100%
McIntosh E. M., Haynes R. H.
Acta Biochimica Polonica
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1996
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tom 43
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nr 4
The enzyme dUTP pyrophosphatase (dUTPase, EC 3.6.1.23) is essential for cellular DNA replication and cell viability by virtue of its role in reducing the availability of dUTP as a substrate for DNA polymerases. Several members of the onco- and lentivirus families of retroviruses encode dUTPases and mutant strains of these viruses defective in this enzyme exhibit suboptimal replication kinetics. Among the lentiviruses there exists a surprising phylogenetic discontinuity in the distribution of dUTPase genes: non-primate viruses (EIAV, CAEV, FIV, visna) contain such genes whereas the primate viruses (HIVs, SIVs) do not The reason for this difference is unknown. We suggest the following explanation: (1) the nuclear and mitochondrial compartmentalization of the mammalian dUTPase, combined with the cytoplasmic location of ribonucleotide reductase, leads to the net synthesis of dUTP, together with dCTP, dGTP and dATP in the cytoplasm; (2) this combination of dNTPs serves as a "toxic cocktail" for viral replication by virtue of its ability to promote the synthesis of uracil-substituted DNA; (3) many viruses have adapted to this challenge by encoding dUTPases that are free of normal cellular regulatory constraints; and (4) the fortuitous expression of a dUTPase encoded by one or more human endogenous retroviruses (HERVs) has led to the evolutionary loss of the putative ancestral dUTPase gene of primate lentiviruses. Thus, we propose that efficient replication of HIV in humans depends upon expression of a dUTPase encoded by an endogenous retrovirus. If this proposal is correct, then the entry of HIV into target cells is necessary, but not sufficient, for replication of the virus in humans.
2

High molecular mass dextran sulfate increases expression of HIV-1 coreceptor CCR-5 in macrophage-monocytes in culture

100%
Jagodzinski P. P., Trzeciak W. H.
Acta Biochimica Polonica
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1998
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tom 45
|
nr 1
It has been reported that high molecular mass dextran sulfate (HMDS) enhances the infection of monocyte-macrophages by HIV-1. We observed that in monocyte-macrophages maintained in the presence of HMDS the expression of HIV-1 coreceptor CCR-5 was increased approximately 5-fold at the transcriptional level. We postulate that the increased expression of CCR-5 might be responsible for HMDS-enhanced infectivity of monocyte-macrophages by HIV-1.
3

Synthesis and anti-HIV properties of novel 6-phenylselenenyl-5-propyluracils

84%
Miazga A., Felczak K., Siwecka M. A., Lipniacki A., Piasek A., Kulikowski T.
Acta Biochimica Polonica
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2007
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tom 54
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nr 4
863-868
Novel 6-phenylselenenyl-5-propyluracils were synthesized from 5-propyluracil with the use of regioselective synthesis to give 1-[(2-hydroxyethoxy)-methyl]-6-phenylselenenyl-5-propyluracil (6), 1-ethoxymethyl-6-phenylselenenyl-5-propyluracil (9) and 1-benzyloxymethyl-6-phenylselenenyl-5-propyluracil (10). Interaction of these compounds with recombinant HIV-1 reverse transcriptase (RT) was evaluated using a non-isotopic colorimetric method. Compounds 9 and 10 exerted potent HIV RT inhibition (IC500.06 and 0.05 μM respectively) while compound 6 showed moderate inhibition (IC50=3.5 μM). Potent anti-HIV-1 activity in MT-2 cells inoculated by a syncythia-in-ducing HIV-1 (cat #3 strain) laboratory isolate was exerted by compounds 9 and 10 (EC500.62 μM and 0.025 μM, respectively), while compound 6 showed only moderate activity (IC50=4.1 μM). In addition, compound 10 showed very good in vitro therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS drug.
4

Interaction of HIV Tat model peptides with tRNA and 5S rRNA

67%
Giel-Pietraszuk M., Barciszewska M. Z., Mucha P., Rekowski P., Kupryszewski G., Barciszewski J.
Acta Biochimica Polonica
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1997
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tom 44
|
nr 3
New data are presented on the interaction of model synthetic peptides con­taining an arginine-rich region of human immunodeficiency virus (HIV-Tat), with native RNA molecules: tRNA Phe of Saccharomyces cerevisiae and 5S rRNA from Lupinas luteus. Both RNA species form complexes with the Tatl (GRKKRRQRRRA) and Tat2 (GRKKRRQRRRAPQDSQTHQASLSKQPA) pep- tides, as shown by electrophoretic gel shift and RNase footprint assays, and CD measurements. The nucleotide sequence UGGG located in the dihydrouridine loop of tRNA Phe as well as in the loop D of 5S rRNA is specifically protected against RNases. Our data indicate direct interactions of guanine of RNA moie­ties with argininc residues. These interactions seem similar to those observed in DNA-protein complexes, but different from those previously observed in the TAR RNA-Tat complexes.
5

Witaminy w diecie osob doroslych HIV-pozytywnych

59%
Lebiedzinska A., Bierzynska N., Lemanska M., Jankowska M., Trocha H., Smiatacz T., Szefer P.
Bromatologia i Chemia Toksykologiczna
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2009
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tom 42
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nr 3
672-677
6

Use of HIV as a gene transfer vector

51%
Pluta K., Kacprzak M. M.
Acta Biochimica Polonica
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2009
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tom 56
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nr 4
531-595
 Despite the extensive research efforts over the past 25 years that have focused on HIV, there is still no cure for AIDS. However, tremendous progress in the understanding of the structure and biology of the HIV virus led to the development of safe and potent HIV-based transgene delivery vectors. These genetic vehicles are referred to as lentiviral vectors. They appear to be better suited for particular applications, such as transgene delivery into stem cells, compared to other viral- and non-viral vectors. This is because Lentivirus-based vectors can efficiently infect nondividing and slowly dividing cells. In the present review article, the current state of understanding of HIV-1 is discussed and the main characteristics that had an impact on vector design are outlined. A historical view on the vector concept is presented to facilitate discussion of recent results in vector engineering in a broader context. Subsequently, a state of the art overview concerning vector construction and vector production is given. This review also touches upon the subject of lentiviral vector safety and related topics that can be helpful in addressing this issue are discussed. Finally, examples of Lentivirus-based gene delivery systems and their applications are presented, with emphasis on animal transgenesis and human gene therapy.
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