Plasmodium falciparum var gene expression homogeneity as a marker of the host-parasite relationship under different levels of naturally acquired immunity to malaria
Warimwe, George M.
Kiragu, Esther W.
Buckee, Caroline O
Musyoki, Jennifer N.
Bull, Peter C.
Public Library of Science
Copyright: © 2013 Warimwe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acquired immunity to Plasmodium falciparum infection causes a change from frequent, sometimes life-threatening, malaria in young children to asymptomatic, chronic infections in older children and adults. Little is known about how this transition occurs but antibodies to the extremely diverse PfEMP1 parasite antigens are thought to play a role. PfEMP1 is encoded by a family of 60 var genes that undergo clonal antigenic variation, potentially creating an antigenically heterogeneous infecting population of parasites within the host. Previous theoretical work suggests that antibodies to PfEMP1 may play a role in "orchestrating" their expression within infections leading to sequential, homogeneous expression of var genes, and prolonged infection chronicity. Here, using a cloning and sequencing approach we compare the var expression homogeneity (VEH) between isolates from children with asymptomatic and clinical infections. We show that asymptomatic infections have higher VEH than clinical infections and a broader host antibody response. We discuss this in relation to the potential role of host antibodies in promoting chronicity of infection and parasite survival through the low transmission season.
PCB and GMW were supported by Wellcome Trust (www.wellcome.ac.uk/)Programme Grants (092741, 084535 and 077092 to PCB and/or KM) and Project Grant (076030 to PCB and KM). GMW was also supported by a Wellcome Trust Strategic Award (084538 to KM). MR is funded by a Royal Society (royalsociety.org/) University Research Fellowship.
Research Support, Non-U.S. Gov't
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