Uracil within DNA: an actor of antiviral immunity

Uracil is a natural base of RNA but may appear in DNA through two different pathways including cytosine deamination or misincorporation of deoxyuridine 5'-triphosphate nucleotide (dUTP) during DNA replication and constitutes one of the most frequent DNA lesions. In cellular organisms, such lesions are faithfully cleared out through several universal DNA repair mechanisms, thus preventing genome injury. However, several recent studies have brought some pieces of evidence that introduction of uracil bases in viral genomic DNA intermediates during genome replication might be a way of innate immune defence against some viruses. As part of countermeasures, numerous viruses have developed powerful strategies to prevent emergence of uracilated viral genomes and/or to eliminate uracils already incorporated into DNA. This review will present the current knowledge about the cellular and viral countermeasures against uracils in DNA and the implications of these uracils as weapons against viruses

APOBEC3 family members and their associated roles in exogenous viruses and endogenous retroelements restriction

Data are compiled from [27, 77, 87, 90, 126-140].<p><b>Copyright information:</b></p><p>Taken from "Uracil within DNA: an actor of antiviral immunity"</p><p>http://www.retrovirology.com/content/5/1/45</p><p>Retrovirology 2008;5():45-45.</p><p>Published online 5 Jun 2008</p><p>PMCID:PMC2427051.</p><p></p

Biosynthesis pathways of ribonucleotides and deoxyribonucleotides in mammalian cells and the possible consequence of the misincorporation and repair of uracil residues in DNA

synthesis of AMP, CMP, GMP and UMP ribonucleotides allows the formation of dATP, dCTP, dGTP, dTTP and dUTP deoxyribonucleotides, which can be readily incorporated in DNA by cellular DNA polymerases. Note that dTTP derives from dUTP hydrolysis. Abbreviations: A, adenine; C, cytosine; G, guanine; T, thymine; U, uracil; MP, monophosphate; DP, diphosphate; TP, triphosphate; rNDP, ribonucleotide diphosphate; NMPK, nucleotide monophosphate kinase; NDPK, nucleotide diphosphate kinase.<p><b>Copyright information:</b></p><p>Taken from "Uracil within DNA: an actor of antiviral immunity"</p><p>http://www.retrovirology.com/content/5/1/45</p><p>Retrovirology 2008;5():45-45.</p><p>Published online 5 Jun 2008</p><p>PMCID:PMC2427051.</p><p></p

Synthesis, in Vitro Antiviral Evaluation, and Stability Studies of Novel α-Borano-Nucleotide Analogues of 9-[2-(Phosphonomethoxy)ethyl]adenine and ( R )-9-[2-(Phosphonomethoxy)propyl]adenine

International audienceWe describe here the synthesis of 9-[2-(boranophosphonomethoxy)ethyl]adenine (6a) and (R)-9-[2-(boranophosphonomethoxy)propyl]adenine (6b), the first alpha-boranophosphonate nucleosides in which a borane (BH3) group substitutes one nonbridging oxygen atom of the alpha-phosphonate moiety. H-phosphinates 5a and 5b and alpha-boranophosphonates 6a and 6b were evaluated for their in vitro activity against human immunodeficiency virus (HIV) infected cells and against a panel of DNA or RNA viruses. Compounds 5a, 5b, 6a, and 6b exhibited no significant antiviral activity in vitro and cytotoxicity. To measure the chemical and enzymatic stabilities of the target compounds 6a and 6b, kinetic data of decomposition for derivatives 5a, 5b, 6a, 6b, and standard compounds were studied at 37 degrees C in several media. The alpha-boranophosphonates 6a and 6b were metabolized in culture medium into H-phosphinates 5a and 5b, with half-live values of 5.3 h for 6a and 1.3 h for 6b

Un système de réparation des uraciles unique chez les virus ARN (Le cas du virus HIV-1)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocCACHAN-ENS (940162301) / SudocSudocFranceF

Un système de réparation des uraciles unique chez les virus ARN (Le cas du virus HIV-1)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocCACHAN-ENS (940162301) / SudocSudocFranceF

Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates

We report synthesis, in vitro antiviral activity, and stability studies in biological media of original boranophosphonate isosteres of AZT and d4T monophophates. A convenient route for the synthesis of 3'-Azido-3'-deoxythymidine-5'-boranophosphonate 8 and 2',3'-Didehydro-3'-dideoxythymidine-5'-boranophosphonate 12 is described. H-phosphinates 7 and 11, and alpha-boranophosphonates 8 and 12 exhibited no significant in vitro activity against HIV-infected cells, neither against a broad panel of viruses, up to 200 microM. The absence of activity of target compounds 8 and 12 can be partially explained by their short half-life in culture medium.status: publishe

Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates

International audienc