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Vector Competence Analyses on Aedes aegypti Mosquitoes using Zika Virus
Published on: May 31, 2020
Infection via mosquito bite alters Zika virus tissue tropism and replication kinetics in rhesus macaques
Dawn M Dudley1, Christina M Newman1, Joseph Lalli2
1Department 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, 53705, USA.
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.
Insights
Mosquito-borne Zika virus (ZIKV) infection in rhesus macaques mimics human disease more closely than needle inoculation. This new model reveals delayed replication and distinct tissue distribution, aiding ZIKV research.
Area of Science:
- Virology
- Infectious Diseases
- Animal Models
Background:
- Current Zika virus (ZIKV) research models use needle inoculation, which may not fully replicate natural transmission.
- The impact of mosquito-borne ZIKV infection on disease progression and viral distribution remains underexplored in nonhuman primates.
Purpose of the Study:
- To develop and validate a mosquito bite-based ZIKV infection model in rhesus macaques.
- To compare ZIKV pathogenesis, viral load dynamics, tissue tropism, and viral genetic diversity between mosquito-borne and needle-inoculated infections.
Main Methods:
- Rhesus macaques were infected with ZIKV via either Aedes aegypti mosquito bites or direct needle inoculation.
- Viral loads were monitored over time, and ZIKV tissue distribution was analyzed post-mortem.
- Deep sequencing was employed to assess viral genetic heterogeneity and diversity.
Main Results:
- Mosquito-borne ZIKV infection led to delayed viral replication and lower peak viral loads compared to needle inoculation.
- ZIKV tissue distribution in mosquito-infected macaques was restricted to hemolymphatic, reproductive, kidney, and liver tissues, resembling human infection patterns.
- Mosquito-borne ZIKV exhibited greater sequence heterogeneity and lower genetic diversity than needle-inoculated ZIKV.
Conclusions:
- Mosquito bite-mediated ZIKV infection in rhesus macaques provides a more relevant model for studying human ZIKV disease.
- This model offers insights into ZIKV pathogenesis, transmission, and viral evolution that are distinct from needle-based inoculation studies.
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