Antigenic evolution of dengue viruses over 20 years

Variations in disease enhancement Secondary Dengue virus (DENV) infections can be dangerous if levels of antibodies from prior infection are inadequate to clear the virus. This RNA flavivirus exploits the presence of lower levels of heterotypic antibodies to infect immunoglobulin Fcγ receptor–bearing cells. Many RNA viruses also exhibit antigenic variation, which classically allows evasion of immune responses. Katzelnick et al . investigated whether antigenic variation in DENV has a biological function in a virus that courts immune responses to enhance replication (see the Perspective by Rohani and Drake). Using antigenic cartography on a panel of more than 400 DENV1-4 subtype samples isolated in Bangkok, Thailand, the authors found that antigenic variation in virus populations oscillated between similarity and dissimilarity across subtypes over time, with outbreaks correlating with periods of antigenic dissimilarity within serotypes. This pattern may be at least in part a result of the conflicting evolutionary pressures of immune evasion and immune enhancement. —CA