Abstract

Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, and vaccines, but they rely on needle inoculation of virus: the effects of mosquito-borne infection on disease outcome have not been explored in these models. Here we show that infection via mosquito bite delays ZIKV replication to peak viral loads in rhesus macaques. Importantly, in mosquito-infected animals ZIKV tissue distribution was limited to hemolymphatic tissues, female reproductive tract tissues, kidney, and liver, potentially emulating key features of human ZIKV infections, most of which are characterized by mild or asymptomatic disease. Furthermore, deep sequencing analysis reveals that ZIKV populations in mosquito-infected monkeys show greater sequence heterogeneity and lower overall diversity than in needle-inoculated animals. This newly developed system will be valuable for studying ZIKV disease because it more closely mimics human infection by mosquito bite than needle-based inoculations.

Details

Title
Infection via mosquito bite alters Zika virus tissue tropism and replication kinetics in rhesus macaques
Author
Dudley, Dawn M 1 ; Newman, Christina M 1 ; Lalli, Joseph 2 ; Stewart, Laurel M 1 ; Koenig, Michelle R 1 ; Weiler, Andrea M 3 ; Semler, Matthew R 1 ; Barry, Gabrielle L 3 ; Zarbock, Katie R 1 ; Mohns, Mariel S 1 ; Breitbach, Meghan E 1 ; Schultz-Darken, Nancy 3 ; Peterson, Eric 3 ; Newton, Wendy 3 ; Mohr, Emma L 4 ; Capuano, Saverio, III 3 ; Osorio, Jorge E 2 ; Shelby L O’Connor 5 ; David H O’Connor 5 ; Friedrich, Thomas C 6 ; Aliota, Matthew T 2   VIAFID ORCID Logo 

1  Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave., Madison, WI, USA 
2  Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, 1656 Linden Dr., Madison, WI, USA 
3  Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Ct., Madison, WI, USA 
4  Department of Pediatrics, University of Wisconsin-Madison, University of Wisconsin Clinical Science Center, 600 Highland Ave, Madison, WI, USA 
5  Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave., Madison, WI, USA; Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Ct., Madison, WI, USA 
6  Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, 1656 Linden Dr., Madison, WI, USA; Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Ct., Madison, WI, USA 
Pages
1-11
Publication year
2017
Publication date
Dec 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-02222-8
ProQuest document ID
1983427447
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.