Variable surface antigen expression, virulence, and persistent infection by Plasmodium falciparum malaria parasites

SUMMARYThe human malaria parasite Plasmodium falciparum is known for its ability to maintain lengthy infections that can extend for over a year. This property is derived from the parasite's capacity to continuously alter the antigens expressed on the surface of the infected red blood cell, thereby avoiding antibody recognition and immune destruction. The primary target of the immune system is an antigen called PfEMP1 that serves as a cell surface receptor and enables infected cells to adhere to the vascular endothelium and thus avoid filtration by the spleen. The parasite's genome encodes approximately 60 antigenically distinct forms of PfEMP1, each encoded by individual members of the multicopy var gene family. This provides the parasite with a repertoire of antigenic types that it systematically cycles through over the course of an infection, thereby maintaining an infection until the repertoire is exhausted. While this model of antigenic variation based on var gene switching explains the dynamics of acute infections in individuals with limited anti-malarial immunity, it fails to explain reports of chronic, asymptomatic infections that can last over a decade. Recent field studies have led to a re-evaluation of previous conclusions regarding the prevalence of chronic infections, and the application of new technologies has provided insights into the molecular mechanisms that enable chronic infections and how these processes evolved.