New Insights into Host Genetic Ancestry as a Risk Factor for Dengue Disease

Dengue is the most important mosquito-borne viral infection of humans worldwide. Genetic ancestry of the host is a significant risk factor for severe dengue, but the mechanisms are not known. Recent findings using human skin explants from genetically defined donors reveal that dengue virus (DENV) replication and spread in skin increases with increasing proportion of European ancestry of the donor, associated with a strong inflammatory response and local myeloid cell infiltration, infection, and migration. In contrast, African ancestry is associated with substantially reduced cutaneous inflammation and cell infiltration following virus inoculation, resulting in reduced infection and migration of infected cells. These findings help explain the long-standing observation that individuals of African descent are relatively protected against severe dengue, while individuals of European descent are not. In this essay, we review DENV infection, focusing on human skin and the influence of genetic ancestry on the cutaneous innate response and virus spread.