Transgene-mediated suppression of the RNA interference pathway inAedes aegyptiinterferes with gene silencing and enhances Sindbis virus and dengue virus type 2 replication

Autor:	J. B. Doty, Alexander W. E. Franz, Ken E. Olson, Cynthia C H Khoo, M. S. Heersink
Rok vydání:	2013
Předmět:	Aedes Sindbis virus fungi Aedes aegypti Dengue virus Biology medicine.disease_cause biology.organism_classification Virology RNA silencing Viral replication RNA interference Insect Science parasitic diseases Genetics medicine Gene silencing Molecular Biology
Zdroj:	Insect Molecular Biology. 22:104-114
ISSN:	0962-1075
DOI:	10.1111/imb.12008
Popis:	RNA interference (RNAi) is the major innate antiviral pathway in Aedes aegypti that responds to replicating arboviruses such as dengue virus (DENV) and Sindbis virus (SINV). On the one hand, the mosquito's RNAi machinery is capable of completely eliminating DENV2 from Ae. aegypti. On the other, transient silencing of key genes of the RNAi pathway increases replication of SINV and DENV2, allowing the viruses to temporally overcome dose-dependent midgut infection and midgut escape barriers (MEB) more efficiently. Here we expressed Flock house virus B2 (FHV-B2) from the poly-ubiquitin (PUb) promoter in Ae. aegypti using the ΦC31 site-directed recombination system to investigate the impact of transgene-mediated RNAi pathway suppression on infections with SINV-TR339eGFP and DENV2-QR94, the latter of which has been shown to be confronted with a strong MEB in Ae. aegypti. FHV-B2 was constitutively expressed in midguts of sugar- and blood-fed mosquitoes of transgenic line PUbB2 P61. B2 over-expression suppressed RNA silencing of carboxypeptidase A-1 (AeCPA-1) in midgut tissue of PUbB2 P61 mosquitoes. Following oral challenge with SINV-TR339eGFP or DENV2-QR94, mean titres in midguts of PUbB2 P61 females were significantly higher at 7 days post-bloodmeal (pbm) than in those of nontransgenic control mosquitoes. At 14 days pbm, infection rates of carcasses were significantly increased in PubB2 P61 mosquitoes infected with SINV-TR339eGFP. Following infection with DENV2-QR94, midgut infection rates were significantly increased in the B2-expressing mosquitoes at 14 days pbm. However, B2 expression in PUbB2 P61 did not increase the DENV2-QR94 dissemination rate, indicating that the infection phenotype was not primarily controlled by RNAi.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::458b3c07587c19405015a065ad265cb7 https://doi.org/10.1111/imb.12008 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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