HIV and HCV Genetic and Phenotypic Variability

HIV AND HCV GENETIC AND PHENOTYPIC VARIABILITY

Principal Investigator: Miguel Ángel Martínez

Presentation

The main goal of our group is to understand the molecular basis underlying HIV-1 and HCV variation and evolution, since a better understanding of the dynamic evolution of these viruses would enable a definition of the factors that contribute to immune evasion, immune persistence and the emergence of variants resistant to new antiviral compounds. The study of viral variation can potentially contribute to the design of new antiviral strategies, given the high mutation rates in HIV and HCV.

A new strategy that we have applied to our study of HIV-1 and HCV is based on use of a novel technology called synthetic attenuated virus engineering (SAVE). SAVE recodes and synthesizes parts of the viral genome, while attenuating virulence and maintaining the amino acid sequence present in the wild virus. SAVE has been successfully used to generate attenuated polio and flu virus vaccines.

Great potential for the development of a new class of live attenuated vaccines, that also adds to our biological knowledge of the virus, is offered by large-scale and low-cost production of the desired DNA sequences and the possibility of recoding the viral genome. Currently underway is preclinical development of live attenuated vaccines for seasonal and pandemic influenza, respiratory syncytial virus and dengue virus. Gene therapy and vaccine vectors can also benefit from synonymous recoding, since deoptimized sequences of the vector may be safer for the host; furthermore, the use of optimized sequences for an antigen or protein would enhance expression levels.

Although synonymous genome recoding has been used primarily with RNA viruses, it can also be used for other organisms and biological systems. For example, in order to design a new generation of live attenuated pneumococcal vaccines, Streptococcus pneumoniae virulence has been attenuated using underrepresented codon pairs to recode the pneumolysin gene.

The study of viruses is a pioneering endeavour in the new research field of synonymous genome recoding and, together with synthetic biology, is giving rise to novel therapies and basic biology applications. Despite great progress in research into viral genome recoding and attenuation, several questions remain unanswered. A key priority in terms of the use of synonymous mutations in biological and clinical contexts would be to decipher the mechanism whereby synonymous mutations affect the virus phenotype.

Keywords: Virus, HIV, HCV, evolution
Principal Investigator

Miguel Ángel Martínez

Miguel Ángel Martínez is the author of 106 peer-reviewed research papers listed in PubMed and of three worldwide patents. He has authored ten book chapters and was guest editor of RNA Interference and Viruses, Current Innovations and Future Trends (Caister...

Curriculum

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