Suppression of Drug Resistance in Dengue Virus

Mateo, Roberto; Nagamine, Claude M.; Kirkegaard, Karla

F or the positive-strand RNA viruses that are considered priority pathogens (dengue virus, West Nile virus, yellow fever virus, Chikungunya virus, severe acute respiratory syndrome coronavirus, hepatitis A virus and the causative agents of several viral encephalopathies), no antiviral pharmaceuticals exist. Among negative-strand RNA viruses, the devastating Ebola outbreak in West Africa and the threat of new influenza virus pandemics further highlight the importance of developing effective vaccines and therapeutics that target any of these highly adaptable, genetically labile RNA viruses (1) . Dengue virus, originally confined to tropical and subtropical areas, has begun to spread outside its former geographic limitations due to the changing ecology of mosquito populations in the face of urbanization and global warming. Previously dengue-free countries are now at risk: Japan, with no reported cases of dengue fever in 70 years, suffered a disease outbreak in 2014 (2) . Due to the expanded range of each of the four dengue virus serotypes, it is now more likely for individuals who have been infected previously with one serotype to become infected with another. Antibodies from the first infection that do not neutralize the newly infecting serotype can enhance its symptoms, increasing the probability of dengue hemorrhagic fever, a severe and often fatal form of the disease (3) . Given the demographics of infection by dengue virus and other emerging pathogens, it is highly desirable to reduce the complexity and expense of vaccines and treatments.