# Immunity to Live Mosquito Probing and Flavivirus Infection in Human Skin

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $293,034

## Abstract

Abstract
Arthropod-borne viruses represent a major threat to humans on a global scale, and of these flaviviruses
transmitted by Aedes aegypti mosquitoes are the most significant risk to human health. Understanding the
immunologic events that take place in the human host, particularly in the skin where virus is transmitted during
mosquito feeding, represents a major gap in our understanding of arbovirus disease. Addressing this gap is a
central theme of the Funding Opportunity PAR-18-860, “Immune Response to Arthropod Blood Feeding”, and
is the goal of the current proposal. To best define these events, we propose a transdisciplinary study between
the Barratt-Boyes lab, with expertise in human skin immunology, and the Vasilakis lab, with expertise in
arbovirology and mosquito-virus-host interactions. The Barratt-Boyes group has established an ex vivo model
of dengue (DENV) and Zika virus (ZIKV) infection in human skin using large-area explants from anonymous
healthy donors, and have defined the immunologic events that occur in skin in the absence of mosquito
probing. The unique access of the Vasilakis group to insectary facilities approved for working with live Aedes
spp. infected with DENV or ZIKV allows us to now explore the contribution of the mosquito to viral
pathogenesis. Thus, we will bring together three essential components – live mosquitoes, human skin, and
pathogenic viruses – to address for the first time the immunologic events that occur during vector-borne
transmission of flaviviruses in human skin. This is a truly innovative proposal; to our knowledge, no
publications exist describing the response of human skin to pathogenic flaviviruses transmitted by live
mosquitoes, and no other research group has an experimental system such as ours to fill this research gap.
We have two specific aims: (1) what is the immune response of human skin to mosquito probing in the
absence of virus, and (2) how does mosquito probing affect DENV and ZIKV replication and spread in human
skin. The results of our study will have a strong and lasting impact on the field of immunology and transmission
of vector-borne pathogens. The work will establish the ex vivo mosquito-skin-virus system as a foundation for
future studies on pathogenesis, therapy and vaccine development.

## Key facts

- **NIH application ID:** 10240340
- **Project number:** 3R21AI147017-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Simon M Barratt-Boyes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,034
- **Award type:** 3
- **Project period:** 2020-05-21 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240340

## Citation

> US National Institutes of Health, RePORTER application 10240340, Immunity to Live Mosquito Probing and Flavivirus Infection in Human Skin (3R21AI147017-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240340. Licensed CC0.

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