The effects of pokeweed antiviral protein on mosquito larvae and arboviruses

Mosquito-borne diseases affect millions of people worldwide each year. Malaria alone kills 1 million people each year, followed by diseases like Yellow Fever which is responsible for up to 30,000 deaths. There are many methods to control the mosquitoes that could be carrying these diseases such as pesticides, mosquito nets, and bug sprays, but each of these methods have serious flaws. New methods need to be developed to better control the spread of these arboviruses. To find these methods, we focus on the transmission of dengue and La Crosse viruses using Aedes albopictus as a model vector. Dengue is a flavivirus that causes up to 50 million infections each year. La Crosse virus causes about 70 cases per year and can lead to encephalitis. We tried a new control method using pokeweed (Phytolacca americana), a native North American plant that is toxic to humans and most animals. Pokeweed produces a ribosome-inactivating protein called pokeweed antiviral protein (PAP), which depurinates the sarcin/ricin loop of the large rRNA in both prokaryotic and eukaryotic ribosomes. It was first shown to be an antiviral agent against Tobacco Mosaic Virus, and has since demonstrated antiviral activity against many DNA and RNA viruses.  We cloned and expressed the active PAP fragment from pokeweed leaves. We reared Aedes albopictus larvae in PAP to see if it would cause mortality and tested PAP against LACV and DENV for virucidal properties. The utility of PAP against mosquito-borne viruses will be discussed.