- 蚊の遺伝子操作研究、人や動物の保護に役立つと研究者が説明 Researcher explains mosquito gene manipulation study, how it might help protect humans, animals
蚊の遺伝子操作研究、人や動物の保護に役立つと研究者が説明 Researcher explains mosquito gene manipulation study, how it might help protect humans, animals
2023-03-13 テキサス A&M大学
黄熱病蚊Aedes aegyptiにおける蚊媒介ウイルスの病原性調節にRNA干渉が必須であること RNA interference is essential to modulating the pathogenesis of mosquito-borne viruses in the yellow fever mosquito Aedes aegypti
Glady Hazitha Samuel,Tyler Pohlenz,Yuemei Dong,Nese Coskun,Zach N. Adelman ,George Dimopoulos,Kevin M. Myles
Proceedings of the National Academy of Sciences Published:March 9, 2023
Models of mosquito-borne disease transmission illustrate that the longevity of the insect vector is a particularly powerful factor in the calculation of basic reproduction number (R0). The mosquito must survive long enough after ingesting the pathogen to deliver infectious bites. Significant levels of pathogen-associated mortality in this host would have a detrimental impact on transmission. Here, we show that Aedes aegypti with a genetic lesion in Dicer-2 are acutely susceptible to multiple viruses associated with human disease, but not other types of infections. Further, we demonstrate that the pathology associated with these infections is primarily controlled through an RNA interference pathway that functions as a resistance mechanism. These results reveal insights into the transmission of many important diseases.
While it has long been known that the transmission of mosquito-borne viruses depends on the establishment of persistent and nonlethal infections in the invertebrate host, specific roles for the insects’ antiviral immune pathways in modulating the pathogenesis of viral infections is the subject of speculation and debate. Here, we show that a loss-of-function mutation in the Aedes aegypti Dicer-2 (Dcr-2) gene renders the insect acutely susceptible to a disease phenotype upon infection with pathogens in multiple virus families associated with important human diseases. Additional interrogation of the disease phenotype demonstrated that the virus-induced pathology is controlled through a canonical RNA interference (RNAi) pathway, which functions as a resistance mechanism. These results suggest comparatively modest contributions of proposed tolerance mechanisms to the fitness of A. aegypti infected with these pathogens. Similarly, the production of virus-derived piwi-interacting RNAs (vpiRNAs) was not sufficient to prevent the pathology associated with viral infections in Dcr-2 null mutants, also suggesting a less critical, or potentially secondary, role for vpiRNAs in antiviral immunity. These findings have important implications for understanding the ecological and evolutionary interactions occurring between A. aegypti and the pathogens they transmit to human and animal hosts.