The RNA Secondary Structure Role in HIV-1 Replication: Study by Molecular Genetics, Phylogeny, and Bioinformatics
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- MED-DIS/Disease Surveillance/Medicine
8 Project completed
Senior Project Manager
Melnikov V G
Institute of Molecular Biology and Genetics, Ukraine, Kiev
- Ivanovsky Institute of Virology, Russia, Moscow
- National Center of Infectious and Parasitic Diseases, Bulgaria, Sofia\nKatholieke Universiteit Leuven / Rega Institute for Medical Research, Belgium, Leuven
Project summaryThe main processes of replication of human immunodeficiency virus type 1 (HIV-1) causing AIDS illness are directed by signal elements located both in untranslated and translated regions of HIV-1 genome, among them are TAR, PolyA, PBS, DIS, SD, Psi, RRE and others. The mechanisms by which HIV-1 signal elements currently known are functioning seem of primary interest and the data available so far are incomplete and even lacking.
The objective of this joint Russian-Ukrainian project is to encourage research on the secondary structure of control elements of HIV-1 genome considering different groups and subtypes of HIV-1 by means of molecular genetics, phylogenetic analysis and RNA structure prediction.
A highly heterogeneity of HIV-1 genome significantly impedes AIDS diagnostics, and on other hand it enables to use phylogenetic approach to study mechanisms of virus replication. By phylogenetic analysis of 750 HIV-1 isolates and prediction of genomic RNAs secondary structures, we have demonstrated that the secondary structure of the region encompassing DIS, SD and Psi hairpins is highly specific for different groups (M, O and N) of HIV-1 and for subtypes C, D, and B of group M. Besides we revealed new variants of DIS, SD and Psi hairpins and showed that the most frequent variants of DIS hairpin (DISLai, DISMal and DISC) tolerate certain base changes.
Our preliminary data on PBS domain proved that phylogenetic approach is also promising for investigation of other control elements in HIV-1 genome. To automatize phylogenetic data processing, we plan to develop database of the secondary structures of control elements directing processes of virus replication (CESSHIV-1 database). The proposed project will be focused on signal elements located in untranslated region of HIV-1 genome. Genomic RNAs of HIV-1 isolates presented in NCBI database and in the Russian collection of HIV-1 strains circulating on the territories of Russia and the Ukraine will be analyzed.
The phylogenetic and structural data on control elements in HIV-1 genomic RNA are believed to contribute to clarification of their functioning mechanisms, choice of successful primers and probes for HIV-1 diagnostics, tracking the course of the global spread of the virus, understanding of HIV-1 drug-resistance mechanisms, etc. The CESSHIV-1 database would be useful for wide range of researchers and physicians engaged in HIV-1 science and for educational and managerial purposes.