Nanotechnology at the service of virology

A group of Spanish scientists, led by researchers from the Center for Astrobiology (CAB, INTA-CSIC), is developing a method based on atomic force microscopy to study the structure of a key region in the genome of the virus. Hepatitis C.

Nanotechnology is a transdisciplinary research field that has allowed the development of experimental systems with which it is possible to analyze matter in the range of dimensions of nanometers, as well as manipulate molecules individually. Its combination with the developments of molecular biology has originated the emerging field of bionanotechnology, with numerous applications in different areas of biophysics, biomedicine, or virology.

Within this approach, in the Laboratory of Molecular Evolution of the Centro de Astrobiología (CAB, INTA-CSIC) has been carried out, in collaboration with a group from Institute of Materials Science of Madrid (CSIC), another of Institute of Parasitology and Biomedicine" López Neyra " (CSIC) and the Center for Biomedical Research in the Network of Liver and Digestive Diseases a> (CIBERehd, ISCIII), a detailed study of the structure of the 5 'end of the RNA genome of hepatitis C virus (HCV), using atomic force microscopy (AFM) technology under various experimental conditions. s.

According to Carlos Briones, coordinator of this work: "the use of AFM has allowed us to analyze for the first time what is the three-dimensional structure (with nanometric resolution) of the 5 'end of the HCV genomic RNA, in the one that is a region of great functional relevance because it is the one that directs the union of the cellular ribosome to the genome of the virus and, therefore, triggers the beginning of the translation of the genetic message of the virus. This functional region is called internal ribosome entry site (or IRES), and we have been able to study it both in its minimal functional sequence and in a longer version that includes the beginning of the coding region of the virus. With this we have detected that in the IRES element, as a consequence of the variation of the concentration of Mg2 + ions in the medium, an RNA-RNA interaction at a distance that in turn promotes a large-scale conformational change ".

In addition, it has been possible to determine that such interaction between remote regions within the IRES is inhibited by the presence in the medium of a microRNA called miR-122, which is fundamental in the replicative cycle of the virus within the hepatocytes. Throughout the work the analysis by AFM has been combined with classical molecular biology methods such as the mobility of RNA in native gels or its degradation controlled by structure-dependent RNase enzymes. All this has made it possible to propose a model on the influence of Mg2 + in the three-dimensional conformation of the HCV IRES.

This application of bionanotechnology to virology represents an important step towards the characterization of an element of great functional relevance in the HCV genome, which could allow identifying in it regions against which it is more efficient to generate interfering molecules that are inhibitors of viral replication. In addition to the repercussions derived from the clinical importance of this virus (which infects 3% of the world population), the study represents a remarkable advance from the point of view of the analysis of the functional nucleic acid structure. This work has been published recently in the journal Nucleic Acids Research .

More information

Scientific article: " A magnesium-induced RNA conformational switch at the internal ribosome entry site of hepatitis C genome virus visualized by atomic force microscopy ", A. García-Sacristán, M. Moreno, A. Ariza-Mateos, E. López-Camacho, RM Jáudenes, Luis Vázquez, Jordi Gómez, J. TO. Martín-Gago, C. Briones. Nucleic Acids Research 2015, 43, 1, 565-580.


Carlos Briones , Researcher at the Department of Molecular Evolution, Center for Astrobiology (CSIC-INTA)

Scientific Culture Unit of the CAB: Luis Cuesta


Fuente: UCC-CAB


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