Genes and Immune History May Shape Dengue and Zika Risk as Climate Warms

Climate change is widely discussed as a driver of mosquito expansion, but a new Perspective article argues that the geography of future dengue, chikungunya, and Zika outbreaks cannot be predicted from temperature and rainfall alone. Writing in Frontiers in Virology, Jelle Heinneman of the University of Amsterdam and Ashley J. Duits of the University Medical Center Groningen and the Red Cross Blood Bank Foundation in Curaçao contend that host susceptibility, shaped by genetics and immune history, must be placed at the center of arboviral risk assessment. Their analysis compares Europe with Latin America and the Caribbean, two regions on opposite ends of the immunological spectrum, and concludes that the same virus arriving in different populations may produce strikingly different epidemics.

The environmental side of the argument is well established. Rising temperatures accelerate mosquito development, survival, biting frequency, and the rate at which viruses replicate inside the insect, while altered rainfall and humidity determine where breeding sites persist. The invasive mosquito Aedes albopictus has expanded across much of temperate Europe, and climate projections indicate substantial growth in the area environmentally suitable for Aedes-borne transmission. Autochthonous outbreaks of dengue and chikungunya have already occurred repeatedly in France and Italy, concentrated in summer and early autumn when vector abundance peaks. Recent modeling suggests climatic suitability for chikungunya transmission in Europe may be broader than previously assumed, raising the probability of future outbreaks. Aedes aegypti, the more efficient vector, remains geographically restricted in Europe, but the continued spread of albopictus is steadily increasing the capacity of some regions to sustain local transmission.

Latin America and the Caribbean present a different picture. Much of the region already experiences widespread arboviral transmission, so climate change is expected less to create new transmission zones than to alter the timing, intensity, and geographic distribution of existing ones, with region-specific increases and decreases in suitability. Seasonal dynamics are strongly modulated by temperature and precipitation, while longer-term fluctuations have been linked to the El Niño-Southern Oscillation. The authors stress that substantial heterogeneity exists within both regions, and that environmental drivers interact with urbanization, land-use change, water management, and human mobility, meaning outbreaks tend to ignite when imported infections coincide with favorable ecological conditions and dense vector populations.

The heart of the Perspective, however, is immunogenetic. Host genetic variation contributes to differences in susceptibility to arboviral infection and severe disease, and the authors emphasize that these differences are polygenic rather than attributable to a few dominant susceptibility genes. Studies of dengue, chikungunya, and Zika have implicated variants involved in viral recognition, interferon signaling, cytokine regulation, Fc-receptor signaling, complement activation, and antigen presentation. Individual effect sizes are often modest, but their combined influence may shape susceptibility and severity across individuals and populations, although the extent of their contribution to population-level disease patterns remains unproven and requires further study.

Regions differ in these immune-related genetic architectures. Many populations in Latin America and the Caribbean are highly admixed, reflecting varying contributions from Indigenous American, African, and European ancestries, and analyses of ancestry-enriched variants suggest that historical infectious pressures have shaped the distribution of alleles involved in cytokine signaling, antigen presentation, and T-cell responses. European populations have experienced distinct demographic and pathogen-driven selective pressures of their own. Experimental work adds biological weight to these observations: one recent study found that genetic ancestry shaped dengue virus infection in human skin explants, with ancestry-associated variation in inflammatory responses and viral replication, indicating that early host-virus interactions may differ between populations even before their population-level consequences are clear.

Human leukocyte antigen variation adds another layer. HLA molecules determine which viral peptides are presented to T cells, making them central to adaptive immunity, and HLA diversity is strongly geographically structured. Associations have been reported between particular HLA alleles and dengue susceptibility and disease severity, but these associations vary across populations, with some showing substantial regional heterogeneity. As transmission expands into Europe, the authors argue, differences in immunogenetic background may contribute to variation in individual susceptibility and severity, though they caution that translating individual-level genetic associations into regional predictions of outbreak size or disease burden is not yet possible with existing data.

Immune history may matter even more than genetics. Pre-existing immunity to arboviruses can protect or harm. In dengue, non-neutralizing or sub-neutralizing antibodies can enhance viral uptake into Fc receptor-bearing cells, a mechanism associated with increased risk of severe disease during secondary heterologous infections, whereas broadly neutralizing antibodies directed against conserved epitopes are protective. Cross-reactive immunity is especially relevant for dengue and Zika because of their antigenic similarity: dengue antibodies can enhance Zika infection in laboratory settings, and cross-reactive responses between the two viruses may either protect or exacerbate disease. Prior exposure can also bias subsequent responses toward previously encountered epitopes, a phenomenon known as original antigenic sin. Beyond antibodies, CD4-positive and CD8-positive T cells contribute to viral clearance and memory, cross-reactive memory T cells have been implicated in both protection and immunopathology, and trained immunity, the epigenetic reprogramming of innate immune cells, may modulate susceptibility in ways that remain poorly understood.

Against this backdrop, the two regions diverge sharply. Many European populations remain largely immunologically naïve to dengue, chikungunya, and Zika because sustained transmission has historically been limited. Viral introductions may therefore encounter populations with little pre-existing immunity, increasing susceptibility, particularly when early transmission goes undetected, as historical dengue expansion in the Americas illustrated. Naïve populations facing chikungunya may also experience substantial burdens of chronic complications, which can persist years after acute infection, as prospective cohort work in Curaçao has documented. Conversely, decades of exposure across Latin America and the Caribbean have generated complex immune landscapes in which sequential infections, coinfections, and immune imprinting mean prior immunity may either protect against infection or contribute to severity depending on exposure history. The authors stress that immunological experience does not necessarily imply lower disease burden; it creates a more intricate susceptibility landscape that must be measured, not assumed.

These differences carry direct consequences for vaccination and preparedness. Dengue vaccines illustrate the challenge, since efficacy and safety depend strongly on pre-existing immunity, and strategies developed and evaluated in endemic, seropositive settings may not transfer directly to largely seronegative European populations. If sustained transmission becomes established in Europe, vaccination policies may need to incorporate serological status, local epidemiology, and population immune history. For chikungunya, vaccine development is advancing rapidly, though questions of long-term safety, effectiveness, and accessibility persist; for Zika, the absence of a licensed vaccine remains a critical gap given the congenital consequences of infection during pregnancy. The authors also call for more representative trial populations, noting that findings from one demographic and epidemiological setting may not generalize to populations with different ancestry compositions or exposure histories.

Preparedness priorities should therefore differ between regions while remaining complementary. In Europe, the emphasis should fall on early detection, outbreak investigation, and rapid response, supported by integrated surveillance systems that combine epidemiological, entomological, and climatic data. In Latin America and the Caribbean, reducing endemic burden requires stronger healthcare infrastructure, expanded access to diagnostics and vaccines, and sustained vector control programs, since historical experience shows how quickly burden can rise when control weakens. Genomic surveillance is expanding in the Americas through Pan American Health Organization initiatives but remains uneven, while long-term ecological and epidemiological studies in Europe are still limited. The authors acknowledge that comparable immunogenetic datasets across both regions are scarce and that uncertainty in climate projections limits the precision of risk estimates. Even so, their central message stands: future arboviral burden will be shaped by the interaction of climate-driven exposure with host genetics, immune memory, and public health capacity, and risk models that ignore host susceptibility will misjudge the epidemics to come, including those posed by emerging threats such as Oropouche virus.

Subject of Research: Genetic and immunological determinants of susceptibility to mosquito-borne viruses under climate change in Europe and Latin America-Caribbean

Article Title: Genetic and immunological determinants of mosquito-borne virus susceptibility and climate change: Europe and Latin America-Caribbean perspectives

Article References: Heinneman, J., & Duits, A. J. (2026). Genetic and immunological determinants of mosquito-borne virus susceptibility and climate change: Europe and Latin America-Caribbean perspectives. Frontiers in Virology, 6, Article 1965985. https://doi.org/10.3389/fviro.2026.1965985

Image Credits: AI Generated

DOI: 10.3389/fviro.2026.1965985

Keywords: dengue, chikungunya, Zika virus, climate change, Aedes mosquitoes, immunogenetics, HLA diversity, immune imprinting, antibody-dependent enhancement, vaccination, public health preparedness, Latin America and the Caribbean