Related Experiment Video
Updated: Jan 6, 2026
15:25
Protocol for Dengue Infections in Mosquitoes A. aegypti and Infection Phenotype Determination
Published on: July 4, 2007
19.0K
New Insights into Host Genetic Ancestry as a Risk Factor for Dengue Disease
Simon M Barratt-Boyes1, Priscila M S Castanha1
1Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
DNA and Cell Biology
|September 22, 2025
Summary
Genetic ancestry influences dengue virus (DENV) infection severity. European ancestry correlates with increased DENV replication and inflammation in skin, while African ancestry shows reduced responses, explaining protection against severe dengue.
Area of Science:
- Virology
- Immunology
- Human Genetics
Background:
- Dengue virus (DENV) is a major global mosquito-borne viral infection.
- Host genetic ancestry is a known risk factor for severe dengue, but underlying mechanisms remain unclear.
- Previous research has not fully elucidated the role of skin immunity in ancestry-related dengue severity.
Purpose of the Study:
- To investigate the impact of human genetic ancestry on dengue virus replication and spread within the skin.
- To explore the relationship between genetic ancestry, cutaneous innate immune responses, and DENV pathogenesis.
- To provide a mechanistic explanation for observed differences in severe dengue risk among diverse ancestral populations.
Main Methods:
- Utilized human skin explants from donors with defined genetic ancestry.
- Inoculated explants with dengue virus (DENV) to assess viral replication and spread.
- Analyzed inflammatory responses, myeloid cell infiltration, infection, and migration in relation to donor ancestry.
Main Results:
- DENV replication and spread in skin explants increased with higher proportions of European ancestry.
- European ancestry was associated with heightened inflammatory responses and increased myeloid cell infiltration, infection, and migration.
- African ancestry correlated with significantly reduced cutaneous inflammation and myeloid cell responses, leading to decreased DENV infection and spread.
Conclusions:
- Host genetic ancestry significantly modulates the cutaneous innate immune response to DENV.
- Differences in skin-level immune reactions and viral spread influenced by ancestry help explain varying risks for severe dengue.
- Findings highlight the critical role of skin immunity and genetic background in dengue pathogenesis.
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