Global selection of Plasmodium falciparum virulence antigen expression by host antibodies


Sci Rep

Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity.

Abdi, A. I., Warimwe, G. M., Muthui, M. K., Kivisi, C. A., Kiragu, E. W., Fegan, G. W., Bull, P. C.

Pages:19882, Volume:6, Edition:1/26/2016, Date,Jan-25


Notes:Abdi, Abdirahman I|Warimwe, George M|Muthui, Michelle K|Kivisi, Cheryl A|Kiragu, Esther W|Fegan, Gregory W|Bull, Peter C|eng|084535/Wellcome Trust/United Kingdom|084538/Wellcome Trust/United Kingdom|092741/Wellcome Trust/United Kingdom|103956/Wellcome Trust/United Kingdom|Research Support, Non-U.S. Gov’t|England|2016/01/26 06:00|Sci Rep. 2016 Jan 25;6:19882. doi: 10.1038/srep19882.

ISBN: 2045-2322 (Electronic)|2045-2322 (Linking) Permanent ID: PMC4726288 Accession Number: 26804201

Author Address: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.|Department of Biochemistry and Chemistry, Pwani University, P.O. Box 195, 80108, Kilifi, Kenya.|The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, OX3 7DQ, UK.|Centre for Research in Therapeutic Sciences and, Institute for Healthcare Management, Strathmore University, P.O. Box 59857-00200 Nairobi, Kenya.|Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3.