Serial passage of a multidrug-resistant clone of Plasmodium fakiparum in concentrations of mefloquine hydrochloride ranging from 30 to 2,400 ng/ml resulted in
African trypanosomes change their antigenicity by successively expressing different members of a group of related but highly diverse proteins, the variant surface glycoproteins (VSGs). We describe a synthetic oligonucleotide that can prime specifically reverse transcription of VSG mRNA out of total trypanosome poly(A)+RNA. The specificity of this priming was verified by cDNA sequence analysis of the transcription products and by the demonstration of variant-specific hybridization of the individual cDNAs to cellular RNA. The oligonucleotide primer also was used as a probe for the conserved sequence found on these VSG mRNAs in trypanosome genomic DNA libraries. A large number of primer-positive clones were detected in a Trypanosoma gambiense genomic library, but very few positive signals were found in a library of Trypanosoma congolense genomic DNA.The parasitic hemoprotozoan Trypanosoma brucei gambiense and related trypanosomes cause potentially fatal disease in both man and domestic animals. The course of infection in most vertebrate hosts is marked by a series of peaks of parasitemia, during which antigenically distinct populations of trypanosomes rise to predominance in the bloodstream. This widespread antigenic variation allows at least a segment of the parasite population to escape the host immune response and, in so doing, accounts for the relapsing nature of the infection (1).There is now a strong body of evidence which suggests that this variation is mediated by the successive expression of genes for different variants of the major surface protein, the variant surface glycoprotein (VSG) (2-4). Studies of unicellular infections indicate that this capacity for antigenic variation exists within individual cells (5), but the mechanism responsible for this selective transcription of one VSG gene at a time remains unclear (reviewed in ref. 6).One particular aspect of the phenomenon of antigenic variation further complicates the immunological and molecular analysis of this process. Although certain VSG serotypes can be shown to predominate early in an infection (7,8), a precise order in the expression of different VSGs is not detectable. Accordingly, one cannot predict which antigenic type will succeed a switch in VSG gene expression, and, because the resulting variant antigen type may express any one of >100 different VSGs (9, 10), the switch in antigen expression can only be detected indirectly by the loss of the preceding antigen.Recent DNA sequence determinations of cDNA clones derived from different VSG mRNAs have revealed a common feature of VSG mRNA structure that is present regardless of the VSG for which the mRNAs code (11)(12)(13)(14). A sequence of 16 nucleotides within the 3' noncoding region of the mRNA adjacent to the addition site for the poly(A) tail is apparently invariant (Fig. 1). We have attempted to exploit this region of homology to develop a means for detecting VSG-specific mRNAs without regard to the coding specificity of the molecules and without the necessity for antigen purifi...
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