[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]
Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes
Lauren B. Carrington a,b,1, Bich Chau Nguyen Tran a, Nhat Thanh Hoang Le a, Tai Thi Hue Luong c, Truong Thanh Nguyen c, Phong Thanh Nguyen c, Chau Van Vinh Nguyen c, Huong Thi Cam Nguyen c, Trung Tuan Vu a, Long Thi Vo a, Dui Thi Le a, Nhu Tuyet Vu a, Giang Thi Nguyen a, Hung Quoc Luu d, Anh Duc Dang d, Timothy P. Hurst e, Scott L. O’Neill e, Vi Thuy Tran a, Duong Thi Hue Kien a, Nguyet Minh Nguyen a, Marcel Wolbers a, Bridget Wills a, and Cameron P. Simmons a,b,e
Author Affiliations: a Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, District 5, Ho Chi Minh City, Vietnam; b Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia; c Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam; d National Institute of Hygiene and Epidemiology, Hai Ba Trung District, Hanoi, Vietnam; e Institute for Vector Borne Disease, Monash University, Clayton, Melbourne, VIC 3168, Australia
Edited by Anthony A. James, University of California, Irvine, CA, and approved November 29, 2017 (received for review September 11, 2017)
In laboratory experiments, Wolbachia (wMel strain)-infected Aedes aegypti are refractory to disseminated arboviral infections. Yet previous characterizations of wMel-mediated blocking have not considered several biologically and ecologically important factors likely to influence the virus–mosquito interaction. After direct feeding on 141 viremic dengue patients, we demonstrate wMel lowers dengue virus (DENV) transmission potential and lengthens the extrinsic incubation period. Subsequently, using established field populations of wild-type and wMel-infected Ae. aegypti, we compared field- versus laboratory-rearing conditions on mosquito susceptibility to disseminated DENV infection. The magnitude of wMel-mediated virus blocking was even greater when mosquitoes developed under field conditions. These clinically and ecologically relevant findings support Wolbachia introgression into Ae. aegypti populations as a biocontrol method to reduce the transmission of DENV and other arboviruses.
The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.
wMel Wolbachia – dengue virus – Aedes aegypti mosquito – extrinsic incubation period – virus transmission
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Author contributions: L.B.C., B.C.N.T., T.T.H.L., T.T.N., P.T.N., C.V.V.N., A.D.D., S.L.O., M.W., B.W., and C.P.S. designed research; B.C.N.T., T.T.H.L., T.T.N., P.T.N., H.T.C.N., and N.M.N. coordinated patient enrollment and sample collection; L.B.C., B.C.N.T., H.T.C.N., T.T.V., L.T.V., D.T.L., N.T.V., G.T.N., H.Q.L., T.P.H., V.T.T., D.T.H.K., and N.M.N. performed research; C.P.S. contributed new reagents/analytic tools; L.B.C., N.T.H.L., and M.W. analyzed data; and L.B.C. and C.P.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1715788115/-/DCSupplemental.
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Keywords: Dengue Fever; Mosquitoes; Aedes Aegypti; Wolbachia.