# How Do Arboviruses Escape the Mosquito Midgut?- Analysis of a Novel Mechanism

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $382,974

## Abstract

Title:
How do arboviruses escape the mosquito midgut? - Analysis of a novel mechanism
Project Summary. Following ingestion of a viremic bloodmeal from a vertebrate host, an
arbovirus enters the midgut lumen of a mosquito vector (such as Aedes aegypti) along with the
bloodmeal. The virus then needs to enter and infect the midgut epithelial cells of the midgut
before the virus disseminates from the midgut to secondary tissues including the salivary
glands. Once these are infected, the mosquito transmits the virus to another vertebrate host
during probing. The molecular nature of the exit mechanism of the virus from the midgut, has
been unresolved so far. In this grant application, we will reveal this mechanism and its genetic
background using a multifaceted portfolio of state-of-the-art methodologies. Our previous
studies demonstrated that during bloodmeal digestion, chikungunya virus (CHIKV) exits the
mosquito midgut via the basal lamina (BL) surrounding the organ. The BL predominantly
consists of collagen IV and laminin and its typical pore size exclusion limit appears to be too
small for virions to pass through. However, during bloodmeal digestion, the BL alters its
structure as midgut-associated collagen IV becomes greatly diminished. We hypothesized that it
is this structural change in the BL that allows virions to exit the midgut during bloodmeal
digestion. In eukaryotes, known proteinases that modify the extracellular matrix including the BL
are matrix metalloproteinases, ADAM/ADAMTS, and serine collagenases. We hypothesize that
these classes of proteinases, which are also present in mosquitoes, are responsible for midgut
BL modification during bloodmeal digestion. To test these two hypotheses, we propose the
following three Specific Aims for this application: 1.) Analyze BL degradation/remodeling and
CHIKV dissemination in Ae. aegypti by ultrastructural studies and proteomic analysis; 2.)
Identify proteinases that are involved in the BL modification process during bloodmeal digestion
and CHIKV dissemination; 3.) Assess whether other viruses (such as Zika, dengue, and Mayaro
viruses) utilize the same midgut escape mechanism as observed for CHIKV and how transgenic
manipulation of proteinase-of-interest expression affects viral midgut escape in mosquitoes.
Completion of these Specific Aims will provide a comprehensive picture explaining the
mechanism of the midgut escape barrier, which key enzymes are involved in the mechanism,
and whether the mechanism elucidated for CHIKV is the paradigm for other arboviruses. Our
results will be critical for developing novel control strategies aimed at manipulating arbovirus
midgut escape in mosquitoes. Our findings will also provide the research community with the
possibility to develop novel genetic markers for vector competence based on midgut escape.

## Key facts

- **NIH application ID:** 9814092
- **Project number:** 5R01AI134661-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Alexander W E Franz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,974
- **Award type:** 5
- **Project period:** 2017-11-03 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9814092

## Citation

> US National Institutes of Health, RePORTER application 9814092, How Do Arboviruses Escape the Mosquito Midgut?- Analysis of a Novel Mechanism (5R01AI134661-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9814092. Licensed CC0.

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