Molecular technology and antigenic variation among intraerythrocytic hemoparasites: do we see reality?

Antigenic variation is one mechanism of immune evasion utilized by many mic roorganisms-encompassing such broad evolutionary groups as viruses, bacteri a, and protozoa-to survive the onslaught of a specifically activated host i mmune system. Because of its importance to the survival of many infectious agents there is considerable interest in understanding this phenomenon. Wit h knowledge of the molecular mechanisms by which these microbes deliberatel y manipulate their genomes, it may be possible to disrupt the molecular mac hinery of the responsible genetic mechanisms. Among intraerythrocytic paras ites, genetic mechanisms that have been observed or postulated to control a ntigenic variation include segmental gene conversion, epigenetically contro lled in situ transcriptional switching, alterations of chromosomal structur e associated with transcriptional control. and recombination during sexual reproduction. Likely, more than one type of mechanism is used by all organi sms that undergo antigenic variation. In this paper, both the observed mech anisms and some of the molecular technology used to detect these mechanisms are discussed. While often seemingly straightforward from a technical stan dpoint, sometimes subtle differences in the methods used to study this proc ess may affect what is observed. Some examples of this phenomenon are discu ssed in the context of a small selection of intraerythrocytic parasites. (C ) 2001 Elsevier Science B.V. All rights reserved.