Longitudinal assessment of Plasmodium falciparum var gene transcription in naturally infected asymptomatic children in Papua New Guinea.

Sequestration and antigenic variation are essential for Plasmodium falciparum survival in vivo contributing to severe pathologic findings and, also, chronic infection. Both are conferred by P. falciparum erythrocyte membrane proteins encoded by ~60 var genes. To study the dynamics of var gene expression, we conducted a 4-month longitudinal study of semi-immune children from Papua New Guinea. By use of magnetic bead-anchored reverse-transcription polymerase chain reaction analysis performed over 5 var regions, as well as cloning and sequencing, the longitudinal distribution of full-length var transcripts was analyzed. We identified a dynamic picture of var gene expression with rapid switches but with identical var transcripts recurring for up to 10 weeks. The number of var transcripts was correlated to the number of infections, with a mean of 1.7 var transcripts identified per sample and infecting strain. Analysis of 158 different Duffy binding-like 1 alpha sequences confirmed the recombinogenic nature of var genes. This is the first report of the dynamics of var gene expression in chronically infected children.