Ashley St. John: Flavivirus immune history as a determinant of future viral infection outcomes (Ad hoc Seminar)

Flavivirus immune history as a determinant of future viral infection outcomes

Flavivirus exposure is increasingly common, and pre-existing flavivirus immunity can shape the outcome of subsequent infections. This is particularly well established for dengue virus (DENV), where prior infection can alter the risk and severity of later disease. Our studies show that these effects extend beyond antibody specificity and involve imprinting of the broader immune program. We will discuss how flavivirus immune history shapes subsequent disease, from the long-term effects of primary DENV immunity innate responses (for example, through mast cells and innate like lymphocytes) on later dengue severity, to the consequences of heterologous flavivirus exposures, including Japanese encephalitis virus followed by DENV, or maternal DENV immunity during congenital Zika virus infection. We will also consider how prior flavivirus exposure may more broadly condition host immunity, influencing disease severity and mortality even during infection with an unrelated virus such as SARS-CoV-2. Together, these examples invite consideration of how innate immune programming during primary infection, the sequence of flavivirus-specific memory generation, and even ongoing immune conditioning in flavivirus-hyperendemic settings can shape outcomes during sequential viral infections.