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High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections

Published online by Cambridge University Press:  06 April 2009

C. M. R. Turner  and
J. D. Barry
C. M. R. Turner
Affiliation:
Department of Zoology, University of Glasgow, Glasgow G12 8QQ
J. D. Barry
Affiliation:
Institute of Genetics, University of Glasgow, Glasgow Gil 5JS
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Summary

Rates at which Trypanosoma brucei rhodesiense trypanosomes switch from expression of one variable antigen type (VAT) to that of another have been determined in cloned populations that have been recently tsetse-fly transmitted. Switching rates have been determined between several, specific pairs of VATs in each population. High rates of switching were observed in 2 cloned trypanosome lines, each derived from a separate cyclical transmission of the same parental stock and each expressing a different major VAT. Five estimates of the switching rate between one particular pair of VATs were consistently high (approximately 1 × 103 switches/cell/generation). These high switching rates were similar both in bloodstream populations of mice and in populations confined to subcutaneously implanted growth chambers in mice, thus indicating that the interaction of the bloodstream population with other trypanosome populations in the lymphatics or extravascular sites in systemic infections did not influence the estimates of the rate of switching. Fourteen estimates were made of VAT-specific switching rates in bloodstream infections involving 8 combinations from among 6 VATs. Switching rate estimates were VAT-specific and showed considerable variation between different combinations of VATs — from 1.9 × 10−6 to 6.9 × 10−3 switches/cel/generation. The rates of switching to different metacyclic-VATs were, however, very similar. Summation of between 3 and 5 VAT-specific switching rate values in each of 4 experiments conducted in bloodstream infections has provided minimum estimates of the overall rate of antigenic variation: 2.0−9.3 × 10−3 switches/cell/generation. These values are between 20 and 66000-fold higher than previously published estimates. It is likely that at least 1 in every 100 trypanosomes switches its VAT expression every generation.

Keywords

Trypanosoma brucei rhodesienseantigenic variationtrypanosome transmissionvariable antigen typescloned populations.
Type
Research Article
Information
Parasitology , Volume 99 , Issue 1 , August 1989 , pp. 67 - 75
Copyright
Copyright © Cambridge University Press 1989

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References

REFERENCES

Askonas, B. A., & Bancroft, G. J., (1984). Interaction of African trypanosomes with the immune system. Philosophical Transactions of the Royal Society of London, B 307, 41–50.Google ScholarPubMed
Barry, J. D., (1986). Antigen variation during Trypanosoma vivax infections of different host species. Parasitology 92, 51–65.CrossRefGoogle ScholarPubMed
Barry, J. D., Crowe, J. S., & Vickerman, K., (1983). Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature, London 306, 699–701.CrossRefGoogle ScholarPubMed
Barry, J. D., & Emery, D. L., (1984). Parasite development and host responses during the establishment of Trypanosoma brucei infection transmitted by tsetse fly. Parasitology 88, 67–84.CrossRefGoogle ScholarPubMed
Barry, J. D., Le Ray, D., & Herbert, W. J., (1979). Infectivity and virulence of Trypanosoma (Trypanozoon) brucei for mice. Journal of Comparative Pathology 89, 465–70.CrossRefGoogle ScholarPubMed
Bernards, A., Van Der Ploeg, L. H. T., Gibson, W. C., Leegwater, P., Eygenraam, F., De Lange, T., Weijers, P., Calafat, J., & Borst, P., (1986). Rapid change in the repertoire of variant surface glycoprotein genes in trypanosomes by gene duplication and deletion. Journal of Molecular Biology 190, 1–10.CrossRefGoogle ScholarPubMed
Borst, P., & Greaves, D. R., (1987). Programmed gene rearrangements altering gene expression. Science 235, 658–67.CrossRefGoogle ScholarPubMed
Cantrell, W., (1958). Mutation rate and antigenic variation in Trypanosoma equiperdum. Journal of Infectious Diseases 103, 263–71.CrossRefGoogle ScholarPubMed
Crowe, J. S., Lamont, A. G., Barry, J. D., & Vickerman, K., (1984). Cytotoxicity of monoclonal antibodies to Trypanosoma brucei. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 508–13.CrossRefGoogle ScholarPubMed
Doyle, J. J., (1977). Antigenic variation in the salivarian trypanosomes. In Immunity to Blood Parasites of Animals and Man (ed. Miller, L. H., Pine, J. A., and McKelvey, J. J.,) pp. 31–64. New York, London: Plenum Press.CrossRefGoogle Scholar
Doyle, J. J., Hirumi, H., Hirumi, K., Lupton, E. N., & Cross, G. A. M., (1980). Antigenic variation in clones of animal-infective Trypanosoma brucei derived and maintained in vitro. Parasitology 80, 359–69.CrossRefGoogle ScholarPubMed
Gray, A. R., (1965). Antigenic variation in clones of Trypanosoma brucei 1. Immunological relationships of the clones. Annals of Tropical Medicine and Parasitology 59, 27–36.CrossRefGoogle Scholar
Hajduk, S. L., Cameron, C. R., Barry, J. D., & Vickerman, K., (1981). Antigenic variation in cyclically transmitted Trypanosoma brucei. Variable antigen type composition of metacyclic trypanosome populations from the salivary glands of Glossina morsitans. Parasitology 83, 595–607.CrossRefGoogle Scholar
Hajduk, S. L., & Vickerman, K., (1981). Antigen variation in cyclically transmitted Trypanosoma brucei. Variable antigen type composition of the first parasitaemia in mice bitten by trypanosome-infected Glossina morsitans. Parasitology 83, 609–21.CrossRefGoogle Scholar
Inverso, J. A., De Gee, A. L. W., & Mansfield, J. M., (1988). Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. Journal of Immunology 140, 289–93.CrossRefGoogle Scholar
Kosinski, R. J., (1980). Antigenic variation in trypanosomes: a computer analysis of variant order. Parasitology 80, 343–57.CrossRefGoogle ScholarPubMed
Lamont, G. S., Tucker, R. S., & Cross, G. A. M., (1986). Analysis of antigen switching rates in Trypanosoma brucei. Parasitology 92, 355–67.CrossRefGoogle ScholarPubMed
Lanham, S. W., & Godfrey, D. G., (1970). Isolation of salivarian trypanosomes from man and other mammals using DEAE-cellulose. Experimental Parasitology 28, 521–34.CrossRefGoogle ScholarPubMed
Maudlin, I., & Dukes, P., (1985). Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies I. Selection of susceptible and refractory lines of Glossina morsitans morsitans. Annals of Tropical Medicine and Parasitology 79, 317–24.CrossRefGoogle ScholarPubMed
Miller, E. N., & Turner, M. J., (1981). Analysis of antigenic types appearing in first relapse populations of clones of Trypanosoma brucei. Parasitology 82, 63–80.CrossRefGoogle ScholarPubMed
Myler, P. J., Allen, A. L., Agabain, N., & Stuart, K., (1985). Antigenic variation in clones of Trypanosoma brucei grown in immune-deficient mice. Infection and Immunity 47, 684–90.CrossRefGoogle ScholarPubMed
Pearson, T. W., Pinder, M., Roelants, G. E., Kar, S. K., Lundin, L. B., Mayor-Whithey, K. S., & Hewett, R. S. (1980). Methods for the derivation and detection of antiparasite monoclonal antibodies. Journal of Immunological Methods 34, 141–54.CrossRefGoogle ScholarPubMed
Seed, J. R., Edwards, R., & Sechelski, J., (1984). T h e ecology of antigenic variation. Journal of Protozoology 31, 48–53.CrossRefGoogle Scholar
Snedecor, G. W., & Cochran, W. G., (1967). Statistical Methods. Ames, Iowa: Iowa State University Press.Google Scholar
Stern, A., Nickel, P., Meyer, T. F., & So, M., (1984). Opacity determinants of Neisseria gonorrhoeae: gene expression and chromosomal linkage to the gonococcal pilus gene. Cell 37, 447–56.CrossRefGoogle Scholar
Stoenner, H. G., Dodd, T., & Larsen, C., (1982). Antigenic variation of Borrelia hermsii. Journal of Experimental Medicine 156, 1297–311.CrossRefGoogle ScholarPubMed
Tait, A., Barry, J. D., Wink, R., Sanderson, A., & Crowe, J. S., (1985). Enzyme variation in T. brucei sspp. II. Evidence for T.b. rhodesiense being a set of variants of T.b. brucei. Parasitology 90, 89–100.CrossRefGoogle Scholar
Turner, C. M. R., Hunter, C. A., Barry, J. D., & Vickerman, K., (1986 a). Similarity in variable antigen type composition of Trypanosoma brucei rhodesiense populations in different sites within the mouse host. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 824–30.CrossRefGoogle ScholarPubMed
Turner, C. M. R., Barry, J. D., & Vickerman, K., (1986). Independent expression of the metacyclic and bloodstream variable antigen repertoires of Trypanosoma brucei rhodesiense. Parasitology 92, 61–12.CrossRefGoogle ScholarPubMed
Van Meirvenne, N., Janssens, P. G., & Magnus, E., (1975). Antigenic variation in syringe passaged populations of Trypanosoma (Trypanozoori) brucei. Rationalization of the experimental approach. Annales de la Société beige de Médicine tropicale 55, 1–23.Google ScholarPubMed
Vickerman, K., (1985). Developmental cycles and biology of pathogenic trypanosomes. British Medical Bulletin 41, 105–14.CrossRefGoogle ScholarPubMed
Watkins, J. F., (1964). Observations on antigenic variation in a strain of Trypanosoma brucei growing in mice. Journal of Hygiene 62, 69–80.CrossRefGoogle Scholar