Antigenic variation at the infected red cell surface in malaria

Many pathogens that either rely on an insect vector to complete their life cycle (e.g., Trypanosoma spp. and Borrelia spp.) or exist in a unique ecolo gical niche where transmission from host to host is sporadic (e.g., Neisser ia spp.) have evolved strategies to maintain infection of their mammalian h osts for long periods of time in order to ensure their survival. Because th ey have to survive in the face of a fully functional immune system, a commo n feature of many of these organisms is their development of sophisticated strategies for immune evasion. For the above organisms and for malaria para sites of the genus Plasmodium, a common theme is the ability to undergo clo nal antigenic variation. In all cases, surface molecules that are important targets of the humoral immune response are encoded in the genome as multic opy, nonallelic gene families. Antigenic variation is accomplished by the s uccessive expression of members of these gene families that show little or no immunological cross-reactivity. In the case of malaria parasites, howeve r, some of the molecules that undergo antigenic variation are also major vi rulence factors, adding an additional level of complication to the host-par asite interaction. In this review, we cover the history of antigenic variat ion in malaria and then summarize the more recent data with particular emph asis on Plasmodium falciparum, the etiological agent of the most severe for m of human malaria.