Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments
ABSTRACT
A previous study, focused on the correlation of muta-tion pairs of synonymous (S) and asynonymous (A) mutations, distinguished only between the treated and untreated data of protease and reverse tran-scriptase (RT) of HIV-1 subtype B. It is well known that single mutation patterns in HIV-1 are treat-ment-specific. It logically follows that covariation between mutations will also be treatment specific. Thus, our motivation is to give a more in depth study of the covariation between mutation pairs, analyzing not only treated and untreated, but what specific treatments were used, and how they affected the co-variation between the mutations differently. We in-tended to further deepen this study by analyzing the covariation of mutations in protease and RT in dif-ferent subtypes of HIV-1. We found that virus sam-ples subjected to antiretroviral Protease- and RT- inhibitors do show different patterns of mutation covariation in B-subtype protease and RT of HIV-1, while maintaining the same overall trend. covariation will tend to be higher and more distinct from and covariation after treatment. The same trend continues in protease and RT re-gardless of subtype. We also found the highly cova-ried codon positions, position pairs, and position- covariation clusters in protease, affected by different treatments. Most of them are well known major drug-resistance sites for these treatments.
A previous study, focused on the correlation of muta-tion pairs of synonymous (S) and asynonymous (A) mutations, distinguished only between the treated and untreated data of protease and reverse tran-scriptase (RT) of HIV-1 subtype B. It is well known that single mutation patterns in HIV-1 are treat-ment-specific. It logically follows that covariation between mutations will also be treatment specific. Thus, our motivation is to give a more in depth study of the covariation between mutation pairs, analyzing not only treated and untreated, but what specific treatments were used, and how they affected the co-variation between the mutations differently. We in-tended to further deepen this study by analyzing the covariation of mutations in protease and RT in dif-ferent subtypes of HIV-1. We found that virus sam-ples subjected to antiretroviral Protease- and RT- inhibitors do show different patterns of mutation covariation in B-subtype protease and RT of HIV-1, while maintaining the same overall trend.
Cite this paper
nullKing, D. , Cherry, R. and Hu, W. (2010) Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments. Journal of Biomedical Science and Engineering, 3, 291-299. doi: 10.4236/jbise.2010.33039.
nullKing, D. , Cherry, R. and Hu, W. (2010) Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments. Journal of Biomedical Science and Engineering, 3, 291-299. doi: 10.4236/jbise.2010.33039.
References
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[1] Wang, Q. and Lee, C. (2007) Distinguishing functional amino acid covariation from background linkage disequilibrium in HIV protease and reverse transcriptase. PLoS ONE, 2(8), 814. [2] Liu, Y., Eyal, E. and Bahar, I. (2008) Analysis of correlated mutations in HIV-1 protease using spectral clustering. Bioinformatics, 24, 1243-1250. [3] Gilbert, P.B., Novitsky, V. and Essex, M. (2005) Covariability of selected amino acid positions for HIV type 1 subtypes C and B. AIDS Research and Human Retroviruses, 21(12), 1016-1030 [4] Hoffman, N.G., Schiffer, C.A. and Swanstrom, R. (2003) Covariation of amino acid positions in HIV-1 protease. Virology, 314, 536-548. [5] Rhee, S.Y., Liu, T.F., Holmes, S.P. and Shafer, R.W. (2007) HIV-1 subtype B protease and reverse transcriptase amino acid covariation. PLoS Computational Biology, 3(5), 87. [6] Hedrick, P. (1987) Gametic disequilibrium measure: proceed with caution. Genetics, 117, 331-341. [7] Rhee, S.Y., Taylor, J., Wadhera, G., Ben-Hur, A., Brutlag, D. and Shafer, R.W. (2006) Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proceedings of the National Academy of Sciences USA. 103, 17355-17360.