Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights
The 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 retrieve...
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Online Access: | https://doi.org/10.4137/BBI.S12093 |
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doaj-ccaf7f06b1be42488c4381f635a1e0712020-11-25T03:06:45ZengSAGE PublishingBioinformatics and Biology Insights1177-93222013-01-01710.4137/BBI.S12093Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic InsightsDiego Frias0Joana P. Monteiro-Cunha1Aline C. Mota-Miranda2Vagner S. Fonseca3Tulio De Oliveira4Bernardo Galvao-Castro5Luiz C. J. Alcantara6Bahia State University, Salvador, Bahia, Brazil.Bahia School of Medicine and Public Health/Bahia Foundation for Science Development, Salvador, Bahia, Brazil.Bahia School of Medicine and Public Health/Bahia Foundation for Science Development, Salvador, Bahia, Brazil.Bahia State University, Salvador, Bahia, Brazil.Africa Centre for Health and Population Studies, Doris Duke Medical Research Institute, Nelson Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.The 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.https://doi.org/10.4137/BBI.S12093 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Diego Frias Joana P. Monteiro-Cunha Aline C. Mota-Miranda Vagner S. Fonseca Tulio De Oliveira Bernardo Galvao-Castro Luiz C. J. Alcantara |
spellingShingle |
Diego Frias Joana P. Monteiro-Cunha Aline C. Mota-Miranda Vagner S. Fonseca Tulio De Oliveira Bernardo Galvao-Castro Luiz C. J. Alcantara Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights Bioinformatics and Biology Insights |
author_facet |
Diego Frias Joana P. Monteiro-Cunha Aline C. Mota-Miranda Vagner S. Fonseca Tulio De Oliveira Bernardo Galvao-Castro Luiz C. J. Alcantara |
author_sort |
Diego Frias |
title |
Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights |
title_short |
Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights |
title_full |
Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights |
title_fullStr |
Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights |
title_full_unstemmed |
Human Retrovirus Codon Usage from tRNA Point of View: Therapeutic Insights |
title_sort |
human retrovirus codon usage from trna point of view: therapeutic insights |
publisher |
SAGE Publishing |
series |
Bioinformatics and Biology Insights |
issn |
1177-9322 |
publishDate |
2013-01-01 |
description |
The 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. |
url |
https://doi.org/10.4137/BBI.S12093 |
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