Journal article
Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans
Proceedings of the National Academy of Sciences - PNAS, v 113(22), pp 6271-6276
31 May 2016
PMID: 27190089
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
SignificanceDuffy-null Africans were thought to be resistant to Plasmodium vivax infection. Recently, P. vivax infection was observed in Duffy-null Africans. This parasite adaptation is potentially a serious public health problem as the majority of African populations are Duffy-null. This article is aimed at understanding whether mutations or DNA expansion in Duffy-binding protein (DBP) contributes to P. vivax Duffy-null infection. Importantly, P. vivax infection in Squirrel monkey has an ability to use an invasion pathway that is independent of the DBPs. Thus, P. vivax may use a different ligand–receptor pair for its infection in Duffy-null Africans, or some Duffy-negative Africans are not null but express a low level of Duffy blood group antigen.
The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand–receptor pairs for invasion.
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Details
- Title
- Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans
- Creators
- Karthigayan Gunalan - National Institutes of HealthEugenia Lo - University of California, IrvineJessica B. Hostetler - National Institutes of HealthDelenasaw Yewhalaw - Jimma UniversityJianbing Mu - National Institutes of HealthDaniel E. Neafsey - Broad InstituteGuiyun Yan - University of California, IrvineLouis H. Miller - National Institutes of Health
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 113(22), pp 6271-6276
- Publisher
- National Academy of Sciences
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000376784600055
- Scopus ID
- 2-s2.0-84971408151
- Other Identifier
- 991022192518904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Multidisciplinary Sciences