Table 1.
Summary of Published Plasmodium falciparum Crosses
| Parent 1 | Parent 2 | Vertebrate Host | # of Unique Recombinant Progeny | Main Findings | Cross [Refs] | ||||
|---|---|---|---|---|---|---|---|---|---|
| Name | Origin (Year) | Phenotypes | Name | Origin (Year) | Phenotypes | ||||
| HB3 | Honduras (1980) | PYRR in vitro | 3D7 | Rwanda (1979)a | PYRS in vitro | Splenectomized chimpanzee | 15 | First to establish that P. falciparum genetic crosses can be conducted in non-human primates and mosquitoes; confirmed causal role of dhfr-ts SNPs in PYR resistance; associated pfmdr1 mutations with parasite response to MFQ. | [123] |
| Dd2 | Indochina (1980) | Verapamil-reversible CQR in vitro | HB3 | Honduras (1980) | Verapamil-irreversible CQS in vitro | Splenectomized chimpanzee | 35 | SNPs in pfcrt mediate CQ resistance; SNPs in pfmdr1 can modulate resistance to CQ; hemoglobin-derived peptide accumulation linked to CQR pfcrt alleles; loci associated with QN response and intracellular accumulation levels; SNPs in dhps mediate resistance to sulfadoxine; high expression of pfmdv-1 is important for gametocyte development; a region on chr. 12 is involved in regulating ABS cell cycle duration; cis and trans transcriptional regulation occur in P. falciparum. | [124] |
| 7G8 | Brazil (1980) | Aotus nancymaee non virulent in vivo | GB4 | Ghana (2000) | Aotus nancymaee - virulent in vivo | Splenectomized chimpanzee | 32 | PfRH5 is involved in ABS P. falciparum invasion of A. nanycmaee; an intergenic region between pfrh2a and pfrh2b is involved in P. falciparum alternative invasion pathways; SNPs in pfcrt and pfmdr1 contribute to resistance to ADQ. | [122] |
| GB4 | Ghana (2000) | CQR in vitro | NF54HT-GFP-luc | Rwanda (1979) | CQS, ARTS in vitro | FRG-NOD huHep mice | 4 | Proof-of-concept that FRG-NOD huHep mice can replace non-human primates for P. falciparum crosses. | [40] |
| 7G8 | Brazil (1980) | NF54HT-GFP-luc | Rwanda (1979) | CQS, ARTS in vitro | FRG-NOD huHep mice | 15 | Findings not yet reported. | [40] | |
| NHP*/ NHP4026 | Thailand-Myanmar border (2007) | CQR in vitro; Delayed clearance (but K13 WT) | NF54(HT-GFP-luc) | Rwanda (1979) | CQS, ARTS in vitro | FRG-NOD huHep mice | 84 | Can use a fresh clinical isolate as a cross parent in the huHep host system; geographical origin of parents may affect inbreeding and allele segregation; regions in chrs. 2, 13, and 14 are differentially selected in AlbuMAX vs serum media for ABS growth. | [40, 121] |
| 803 | Cambodia (2009–10) | Delayed clearance | GB4 | Ghana (2000) | ARTS in vitro | Splenectomized Aotus monkey | 27 | AS-treated K13 C580Y and C580 progeny showed similar in vivo clearance t1/2 in artemisinin-treated Aotus monkeys. | [44] |
| NHP1337 | Thailand-Myanmar border (2011) | Delayed clearance | MKK2835 | Thailand-Myanmar border (2003) | ARTS in vitro | FRG-NOD huHep mice | 60 | Geographical origin of parents may affect inbreeding and allele segregation; regions on chrs. 12 and 14 may compensate for ABS ARTR-associated fitness defects. | [39] |
a
The origin of 3D7, a clone of NF54, was recently mapped to Rwanda [36].
ABS, asexual blood stage; ADQ, amodiaquine; ART, artemisinin-resistant; ART, artemisinin-sensitive; chr., chromosome; CQ, chloroquine; GFP, green fluorescent protein; luc, luciferase; MFQ, mefloquine; PYR, pyrimethamine; QN, quinine; SNP, single nucleotide polymorphism