Human retrovirus codon usage from tRNA point of view: therapeutic insights

dc.creatorFrias, Diego
dc.creatorCunha, Joana Paixão Monteiro
dc.creatorMiranda, Aline Cristina Andrade Mota
dc.creatorFonseca, Vagner de Souza
dc.creatorOliveira, Tulio de
dc.creatorCastro Filho, Bernardo Galvão
dc.creatorAlcantara, Luiz Carlos Júnior
dc.date2014-11-13T16:37:27Z
dc.date2014-11-13T16:37:27Z
dc.date2013
dc.date.accessioned2023-09-26T20:13:27Z
dc.date.available2023-09-26T20:13:27Z
dc.identifierFRIAS, D. G. et al. Human retrovirus codon usage from tRNA point of view: therapeutic insights. Bioinformatics and Biology Insights, v. 7, p. 335-345, 2013.
dc.identifier1177-9322
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/8832
dc.identifier10.4137/BBI.S12093
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8851805
dc.descriptionThe purpose of this study was to investigate the balance between transfer ribonucleic acid (tRNA) supply and demand in retrovirus-infected cells, seeking the best targets for antiretroviral therapy based on the hypothetical tRNA Inhibition Therapy (TRIT). Codon usage and tRNA gene data were retrieved from public databases. Based on logistic principles, a therapeutic score (T-score) was calculated for all sense codons, in each retrovirus-host system. Codons that are critical for viral protein translation, but not as critical for the host, have the highest T-score values. Theoretically, inactivating the cognate tRNA species should imply a severe reduction of the elongation rate during viral mRNA translation. We developed a method to predict tRNA species critical for retroviral protein synthesis. Four of the best TRIT targets in HIV-1 and HIV-2 encode Large Hydrophobic Residues (LHR), which have a central role in protein folding. One of them, codon CUA, is also a TRIT target in both HTLV-1 and HTLV-2. Therefore, a drug designed for inactivating or reducing the cytoplasmatic concentration of tRNA species with anticodon TAG could attenuate significantly both HIV and HTLV protein synthesis rates. Inversely, replacing codons ending in UA by synonymous codons should increase the expression, which is relevant for DNA vaccine design
dc.formatapplication/pdf
dc.languageeng
dc.publisherLibertas Academicas
dc.rightsopen access
dc.subjectCodon usage
dc.subjecttRNA
dc.subjectHIV
dc.subjectHTLV
dc.subjectTherapy
dc.titleHuman retrovirus codon usage from tRNA point of view: therapeutic insights
dc.typeArticle


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