SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes

Abstract

The surfaces of the infected erythrocyte (IE) and the merozoite, two developmental stages of malaria parasites, expose antigenic determinants to the host immune system. We report on surface-associated interspersed genes (surf genes), which encode a novel polymorphic protein family, SURFINs, present on both IEs and merozoites. A SURFIN expressed in 3D7 parasites, SURFIN4.2, was identified by mass spectrometric analysis of peptides cleaved off the surface of live IEs with trypsin. SURFINs are encoded by a family of 10 surf genes, including three predicted pseudogenes, located within or close to the subtelomeres of five of the chromosomes. SURFINs show structural and sequence similarities with exported surface-exposed proteins (PvSTP1, PkSICAvar, PvVIR, Pf332, and PfEMP1) of several Plasmodium species. SURFIN4.2 of a parasite other than 3D7 (FCR3S1.2) showed polymorphisms in the extracellular domain, suggesting sequence variability between genotypes. SURFIN4.2 not only was found cotransported with PfEMP1 and RIFIN to the IE surface, but also accumulated in the parasitophorous vacuole. In released merozoites, SURFIN4.2 was present in an amorphous cap at the parasite apex, where it may be involved in the invasion of erythrocytes. By exposing shared polymorphic antigens on IEs and merozoites, the parasite may coordinate the antigenic composition of these attachment surfaces during growth in the bloodstream.

Transcriptional variation in the malaria parasitePlasmodium falciparum

“…Other genes were not part of any of the variant gene families included in Table 1, but also showed clonally variant gene expression. Among those, there were 14 genes encoding exported proteins (Sargeant et al 2006); the gene eba-140 (MAL13P1.60) and the pseudogene Pf Rh3 (PFL2520w) from families linked to erythrocyte invasion (Cortés 2008); surfin4.1 (PFD0100c) (Winter et al 2005); three genes encoding putative Zn-finger proteins; genes related with gametocyte formation, for which expression levels in asexual parasites may determine the propensity to enter sexual differentiation (Supplemental Results); two more enzymes linked to lipid metabolism (beta-hydroxyacyl-ACP dehydratase and dephospho-CoA kinase); and 43 genes encoding proteins annotated as ''unknown function'' (Supplemental Table S2). …”

Stable allele frequency distribution of the polymorphic region of SURFIN4.2 in Plasmodium falciparum isolates from Thailand

“…SURFIN 4.2 also accumulates in the parasitophorous vacuole, and can be detected in an amorphous cap at the newly released merozoite apex, suggesting that it may have a role in the erythrocyte invasion [3]. Such molecules are expected to be under a strong host immune pressure, and indeed the extracellular region is polymorphic between 3D7 and FCR3 parasite lines [3]. Recently, a population genetics-based analysis using Kenyan P. falciparum isolates detected positive diversifying selection and linkage disequilibrium with a distance of ~1.5 kb [5] on surf 4.2 exon 1 encoding the extracellular region.…”

“…SURFIN 4.2 is co-transported to Maurer's clefts with PfEMP-1 and RIFIN, and is expected to be translocated to the erythrocyte membrane for surface exposure. SURFIN 4.2 also accumulates in the parasitophorous vacuole, and can be detected in an amorphous cap at the newly released merozoite apex, suggesting that it may have a role in the erythrocyte invasion [3]. Such molecules are expected to be under a strong host immune pressure, and indeed the extracellular region is polymorphic between 3D7 and FCR3 parasite lines [3].…”

“…The intracellular WRD of SURFIN/PvSTP shares homology with the intracellular region of the other parasite-encoded erythrocyte surface ligands, such as the P. falciparum PfEMP-1 family and P. knowlesi surface variant antigen SICAvar family. Thus, it is possible that the pir gene products have evolved from the extracellular region of SURFIN/PvSTP type proteins, and, similarly, PfEMP-1 and SICAvar proteins may be derived from the extracellular region [3]. SURFIN 4.2 is co-transported to Maurer's clefts with PfEMP-1 and RIFIN, and is expected to be translocated to the erythrocyte membrane for surface exposure.…”

“…Parasite adhesins expressed on the surface of malaria-infected erythrocytes provide adhesive properties and at the same time allow for host immune evasion by virtue of antigenic variation and antigenic polymorphism [2]. Recently, a new multigene family called surf was identified, consisting of at least 10 members in the genome of P. falciparum 3D7 parasite line and infected erythrocyte surface localization was shown for one of the member, SURFIN 4.2 (gene ID: PFD1160w, chr 4) [3]. All SURFIN members are predicted to be type 1 transmembrane proteins and share a similar protein makeup, containing a conserved cysteine-rich domain (CRD) in the N-terminal of their extracellular region, and tryptophan-rich domains (WRD) in the C-terminal predicted intracellular region.…”