Acta Leidensia最新文献

A 235 kD rhoptry protein produced by the malaria parasite, Plasmodium yoelii is the target of antibodies that protect mice against blood-stage challenge with the virulent YM strain. In the protected animals the parasites are confined to reticulocytes and the course of parasitaemia is reminiscent of an avirulent 17X strain infection. The DNA coding for the rhoptry protein has been identified as a multigene family containing at least four members. Sequence analysis of short DNA clones has identified the C-terminus of the protein; a preliminary analysis of longer clones confirms that the genes are polymorphic. The possible implications of these findings for the biology of the parasite are discussed.

Clones of Plasmodium alter their antigenic profile or invasion phenotype when presented with specific challenges. Two examples are reviewed which may represent different genetic mechanisms of adaptation to selection pressures. In one series of experiments, rhesus monkeys were vaccinated with a 143,000/140,000 Mr P. knowlesi merozoite surface protein and then infected with a parasite clone expressing this protein. Primary parasitemia was controlled, but subsequent waves of parasitemia developed from populations of parasites harboring mutations in the 143,000/140,000 Mr gene. Mutations in this gene may be occurring at a continual low rate in the population (as with any normal gene) and particular mutations may have been selected in the vaccinated monkeys. In other experiments, P. falciparum parasite lines were selected from a clone (Dd2) that initially exhibited low rates of invasion into erythrocytes made sialic-acid deficient by neuraminidase treatment. After several growth cycles in neuraminidase-treated erythrocytes, a switch was observed and parasite lines were recovered that invaded neuraminidase-treated and normal erythrocytes at the same rate. The switch mechanism in invasion may represent another aspect of genetic variation, i.e. a programmed response in which certain genes are activated or rearranged. Vaccine trials in the future should include studies on the selection of mutations in the target antigen. Where switching mechanisms exist, knowledge of the genetic mechanisms that produce these adaptive responses will advance analysis of prospective vaccine candidates and contribute to our understanding of parasite biology.

Using minisatellite DNA probes and various Southern blots containing DNA samples from rodent malaria parasites it was shown that minisatellite-like sequences occur in the genome of these Plasmodium species. In contrast to the high copy number as observed in higher eukaryotes, the use of fingerprinting techniques on DNA from these parasites reveals that minisatellite sequences are only present at a small number of loci. When parasite lines which differ in biological parameters are compared, no frequent restriction fragment length polymorphism (RFLP) is observed. Screening data banks revealed the presence of repeated copies of one of the probes, which has the monomer sequence CAGGTGG, in the DNA encoding the immunodominant peptide repeat region of the circumsporozoite (CS) protein from a Plasmodium cynomolgi strain. Comparing the sequences for the CS protein from a number of strains of P. cynomolgi revealed that the core region of the repeats, though subject to limited variation, shares homology to the bacterial recombination signal sequence Chi (GCTGGTGG). The implications of the above findings for genetic variation in malaria parasites and evolution of minisatellite sequences will be discussed.