Retroviruses are universally recognized as human and animal pathogens that induce severe diseases. Because of their remarkable high frequency of genetic recombination retroviral, genomes result in a high level of polymorphisms. Such plasticity originates variants that are resistant to drugs or vaccines. The current treatments for retroviral infection are not effective because they do not inactivate retroviruses, and most of the drugs and vaccines are toxic to cells and produce severe side effects. Therefore, the need to develop a new strategy to interfere with viral infection and replication is urgent. Thus, the main goal is to develop a new in vitro model system in mammalian cell lines that could be resistant to retroviral infection and possibly other viruses. We will accomplish this goal by constructing and introducing into mammalian cells an expression vector that contains an inducible mammalian retroviral promoter fused to a hybrid gene. The hybrid gene will harbor the yeast Ty retrotransposon containing the TYA region and a fragment of the TYB region. These regions, coding for the capsid protein required for virus-like particle (VLP) formation and a protease, respectively, will be fused to the coding region of the enzyme Staphylococcal nuclease which is calcium dependent and inactivates viral nucleic acids.Awardee's statement of the potential commercial applications of the research: We will provide an in vitro model system for combating viral infections in Phase I. A gene construct encoding a hybrid protein capable of interfering with the replication of retroviral particles has the potential of being used as a new form of HIV treatment (Phase 11). This model can be translated into a clinically useful procedure which can be implemented to treat already HIV infected individuals where its purpose will be therapeutic.National Institute of Allergy and Infectious Diseases (NIAID)
