dengue virus infection of the aedes aegypti salivary gland and chemosensory apparatus induces genes that modulate infection and blood-feeding behavior登革热病毒感染的埃及伊蚊唾腺和化学感应的设备感染诱发基因调节和食血的行为.pdfVIP

Dengue Virus Infection of the Aedes aegypti Salivary Gland and Chemosensory Apparatus Induces Genes that Modulate Infection and Blood-Feeding Behavior ´ Shuzhen Sim, Jose L. Ramirez, George Dimopoulos* W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (DENV) transmission. It produces numerous immune factors, as well as immune-modulatory, vasodilatory, and anti- coagulant molecules that facilitate blood-feeding. To assess the impact of DENV infection on salivary gland physiology and ¨ function, we performed a comparative genome-wide microarray analysis of the naıve and DENV infection-responsive A. aegypti salivary gland transcriptomes. DENV infection resulted in the regulation of 147 transcripts that represented a variety of functional classes, including several that are essential for virus transmission, such as immunity, blood-feeding, and host- seeking. RNAi-mediated gene silencing of three DENV infection-responsive genes - a cathepsin B, a putative cystatin, and a hypothetical ankyrin repeat-containing protein - significantly modulated DENV replication in the salivary gland. Furthermore, silencing of two DENV infection-responsive odorant-binding protein genes (OBPs) resulted in an overall compromise in blood acquisition from a single host by increasing the time for initiation of probing and the probing time before a successful bloodmeal. We also show that DENV established an extensive infection in the mosquito’s