Chikungunya virus (CHIKV), an alphavirus in the Togaviridae family, is an important and dangerous viral pathogen that has spread around the world in recent years. CHIKV causes chikungunya fever and severe arthralgia that may persist for several months. Like Dengue Virus (DENV), CHIKV is also an arthropod-borne virus (arbovirus). Currently, no licensed vaccine or drug is available for human use for Chikungunya virus. We have recently developed a novel technology that is based on rational, computer-aided gene design, termed Synthetic Attenuated Virus Engineering (SAVE), to attenuate plus and minus strand RNA viruses (poliovirus, influenza virus dengue virus) by recoding their their genomes to introduce unfavored codon pairs. Those codon pair deoptimized viruses were all successfully attenuated both in tissue culture and in an animal model. Here, we propose to extend the SAVE approach to this emerging and dangerous viral pathogen, Chikungunya virus, to pursue the isolation of an attenuated viral strain. With the aid of computers and specifically tailored algorithms we will recode the genome of CHIKV such that it will contain large segments (encoding either the proteins nsP4, E2, E1) of codon pairs dis-favored in mammals. Based on our previous studies we expect that these recoded CHIK viruses will be similarly attenuated and will serve as possible live vaccine candidates
Chikungunya virus (CHIKV) is an important and dangerous viral pathogen that has spread around the world in recent years. In the 2005-2006 chikungunya fever epidemic in the Indian Ocean island of La Reunion millions of people have been infected in more than 40 countries including India, Malaysia, Indonesia, Thailand, Singapore, the United States, and some European countries. The virus and associated disease were named from clinical symptoms: ?chikungunya? means ?stooped walk? in the local language, and refers to painful arthralgia that can last for months. Other clinical symptoms are similar to those of dengue fever, including fever, nausea, myalgia and rash. Since its discovery, CHIKV has been somewhat ignored by scientists except when it has caused large human outbreaks. There is a risk that the virus will be imported to new areas by infected travelers. CHIKV is transmitted to humans from infected non-human primates and other humans by the bite of Aedes mosquitoes. Evidence exists that CHIKV can also be passed from an infected mother to a developing foetus. Furthermore, inhalation of aerosolized CHIKV in a laboratory setting may lead to CHIKV infection. There is no vaccine to prevent or medicine to treat chikungunya virus infection. Our aim is to develop a novel live vaccine candidate to prevent CHIKV disease, using a specific recoding design of its RNA genome, based on our recent highly successful studies with other plus and minus strand RNA viruses.
