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Plasmodium falciparum  erythrocyte membrane protein 1 (PfEMP1), encoded by the  var  gene family, plays a crucial role in disease virulence through its involvement in binding to various host cellular receptors during infection. Growing evidence suggests that differential expression of the various  var  subgroups may be involved in parasite virulence. To further explore this issue, we have collected isolates from symptomatic patients in south China-Myanmar border, and characterized their sequence diversity and transcription profiles over time of  var  gene family, and cytoadherence properties from the time of their initial collection and extending through a two month period of adaptation to culture. Initially, we established a highly diverse, DBLα (4 cysteines) subtype-enriched, but unique local repertoire of  var -DBL1α sequences by cDNA cloning and sequencing. Next we observed a rapid transcriptional decline of  upsA - and  upsB -subtype  var  genes at ring stage through qRT-PCR assays, and a switching event from initial ICAM-I binding to the CD36-binding activity during the first week of adaptive cultivation  in vitro . Moreover, predominant transcription of  upsA var  genes was observed to be correlated with those isolates that showed a higher parasitemia at the time of collection and the ICAM-1-binding phenotype in culture. Taken together, these data indicate that the initial stage of adaptive process  in vitro  significantly influences the transcription of virulence-related  var  subtypes and expression of PfEMP1 variants. Further, the specific upregulation of the  upsA var  genes is likely linked to the rapid propagation of the parasite during natural infection due to the A-type PfEMP1 variant-mediated growth advantages.

From In Vivo to In Vitro: Dynamic Analysis of Plasmodium falciparum var Gene Expression Patterns of Patient Isolates during Adaptation to Culture