---
title: "Upd-mediated activation of mosquito JAK/STAT restricts ZIKV, DENV, and SINV infection"
id: "biorxiv-2-engineering-upd-like-to-broadly-restrict-arbovirus-infection-and-vector"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-2-engineering-upd-like-to-broadly-restrict-arbovirus-infection-and-vector"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.23.761461v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Upd-mediated activation of mosquito JAK/STAT restricts ZIKV, DENV, and SINV infection
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-2-engineering-upd-like-to-broadly-restrict-arbovirus-infection-and-vector
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.23.761461v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The authors identified **Upd** in Aedes aegypti as an endogenous activator of **JAK/STAT** signaling that limits arbovirus infection in the mosquito vector. - Loss-of-function increased midgut infection and systemic dissemination for the flaviviruses **ZIKV** and **DENV**, and for the alphavirus **SINV**; the manuscript reports higher viral burden and spread after Upd deficiency. - Midgut overexpression of **Upd**, timed to blood feeding, reduced infection by **ZIKV** and **SINV**; blood-meal inducible expression was effective as a temporally targeted antiviral measure. - Mechanistic assays indicated that **Upd** associates with the extracellular region of the **Domeless (Dome)** receptor and that Upd deficiency reduced STAT phosphorylation and STAT nuclear accumulation in the midgut. - Endogenous **Upd** expression rose transiently after an uninfected blood meal and remained elevated after **ZIKV** challenge, linking feeding-associated physiology to sustained antiviral signaling during infection. - In mammal–mosquito transmission models, **Upd** overexpression reduced viral acquisition from infected hosts; conversely, Upd loss enhanced dissemination and raised transmission after systemic infection. - The paper presents a proof of principle: temporally targeted Upd expression can lower arbovirus susceptibility and vector competence in Aedes aegypti. - The source did not report specific molecular dosing, kinetics beyond transient versus sustained expression, nor details of long-term ecological impacts or field deployment strategies; those remain unaddressed in this report.
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Xinjun Tao 1 Zhejiang University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Xinjun%2BTao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Tao%20X&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AXinjun%2BTao%2B) Wenfeng He 1 Zhejiang University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Wenfeng%2BHe%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=He%20W&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWenfeng%2BHe%2B) Huijun Zhang 2 Fudan University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Huijun%2BZhang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zhang%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHuijun%2BZhang%2B) Yan Zhang 1 Zhejiang University; 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Here, we identify Aedes aegypti Upd as an activator of JAK/STAT signaling that restricts arbovirus infection. Loss of Upd increased infection and dissemination of the flaviviruses ZIKV and DENV, as well as the alphavirus SINV, whereas blood meal inducible midgut overexpression reduced ZIKV and SINV infection. Mechanistically, Upd associated with the extracellular region of the Domeless (Dome) receptor, and Upd deficiency markedly reduced STAT phosphorylation and nuclear accumulation in the midgut. Upd expression was transiently induced in the midgut by an uninfected blood meal but remained elevated following ZIKV challenge, linking physiological responses to blood feeding with antiviral defense. In mammal mosquito transmission models, Upd overexpression reduced viral acquisition from infected hosts, whereas Upd deficiency enhanced viral dissemination and increased transmission following systemic infection. Together, these findings identify Upd as an endogenous regulator of mosquito JAK/STAT signaling and provide proof of principle that temporally targeted Upd expression can reduce arbovirus susceptibility and vector competence. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.23.761461v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/24/2026.10.23.761461.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.23.761461v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Engineering Upd-like to broadly restrict arbovirus infection and vector competence in mosquitoes Xinjun Tao, Wenfeng He, Huijun Zhang, Yan Zhang, Jianan Hao, Yixuan Huang, Fangming Xiang, Lu Liu, Raghda Nasser, Erol Fikrig, Nicolas Buchon, Xiaotian Tang bioRxiv 2026.10.23.761461; doi: https://doi.org/10.64898/2026.10.23.761461 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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