Common surface-antigen var genes of limited diversity expressed by Plasmodium falciparum placental isolates separated by time and space.

Abstract

Plasmodium falciparum placental parasites from Cameroon have been shown to express surface variant var genes encoding Duffy binding-like (DBL)-gamma domains that bind chondroitin sulfate A. All 5 domains exhibited sequences with 39%-55% amino acid (aa) identities and appear sufficiently conserved to function in receptor binding. Transcripts of 2 samples showed complete conservation over 4 kb, demonstrating for the first time distinct conserved placental var genes. Four placental isolates from Gabon collected 4 years later expressed DBL-gamma sequences with 85%-99% aa identities to those from Cameroon, confirming the conserved nature of placental variants separated by time and location. Five peripheral parasites from children also displayed DBL-gamma sequences with 75%-97% homologies. From this, it can be concluded that P. falciparum parasites expressing unique var DBL-gamma genes can cause placental malaria, referred to as varPAM genes. This demonstration of structurally/functionally constrained DBL-gamma chondroitin sulfate A-binding domains is relevant to understanding pregnancy-associated malaria pathogenesis and to vaccine development.