Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-19T01:53:49.206Z Has data issue: false hasContentIssue false
  • English
  • Français

Replication slippage and the dynamics of the immune response in malaria: a formal model for immunity

Published online by Cambridge University Press:  29 July 2005

G. DODIN  and
P. LEVOIR
G. DODIN
Affiliation:
Université Denis Diderot, ITODYS, 1 Rue Guy de la Brosse, 75005 Paris, France
P. LEVOIR
Affiliation:
Université Denis Diderot, ITODYS, 1 Rue Guy de la Brosse, 75005 Paris, France
Get access Rights & Permissions [Opens in a new window]

Abstract

A simple mathematical model of the dynamics of malaria invasion is proposed. The model is based on the hypothesis that replication slippage (slipped strand mispairing occurring in replicating DNAs), likely to take place within regular, low-complexity, regions of the plasmodium genome, is a significant mechanism of the ability for the parasite to escape the host immune defence. The model reconciles the conclusions of other formal approaches like periodic bursts of parasitaemia and, in particular, it predicts that antibody cross-reactivity affects the level and the time profile of malaria recrudescence. It also suggests that an efficient strategy for the parasite to escape host humoral immune defences is to express a single antigen. Linking local complexity to antigenic variability tentatively allows prediction of new potentially immunogenic sequences in the plasmodium genome.

Keywords

Plasmodium falciparummathematical modelimmunity
Type
Research Article
Information
Parasitology , Volume 131 , Issue 6 , December 2005 , pp. 727 - 735
Copyright
© 2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alonso, P. L., Sacarlal, J., Aponte, J. J., Leach, A., Macete, E., Milman, J., Mandomando, L., Spiessens, B., Guinovart, C., Espasa, M., Bassat, Q., Aide, P., Ofori-Anyinam, O., Navia, M. M., Corachan, S., Ceuppens, M., Dubois, M., Demoitié, M., Dubovsky, F., Menéndez, C., Tornieporth, N., Ballou, W. R., Thompson, R. and Cohen, J. ( 2004). Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364, 1411–1420.CrossRefGoogle Scholar
Antia, R., Nowak, M. A. and Anderson, R. M. ( 1996). Antigenic variation and the within-host dynamics of parasites. Proceedings of the National Academy of Sciences, USA 93, 985–989.CrossRefGoogle Scholar
Bowman, S., Lawson, D., Basham, D., Brown, D., Chillingworth, T., Churcher, C. M., Craig, A., Davies, R. M., Devlin, K., Feltwell, T., Gentles, S., Gwilliam, R., Hamlin, N., Harris, D., Holroyd, S., Hornsby, T., Horrocks, P., Jagels, K., Jassal, B., Kyes, S., Mclean, J., Moule, S., Mungall, K., Murphy, L., Oliver, K., Quail, M. A., Rajandream, M. A., Rutter, S., Skelton, J., Squares, R., Squares, S., Sulston, J. E., Whitehead, S., Woodward, J. R., Newbold, C. and Barrell, B. G. ( 1999). The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature, London 400, 532–538.CrossRefGoogle Scholar
Chen, Q., Fernandez, V., Sundstrom, A., Schlichtherle, M., Data, S., Hagblom, P. and Wahlgren, M. ( 1998). Developmental selection of var gene expression in Plasmodium falciparum. Nature, London 394, 392–395.CrossRefGoogle Scholar
Dodin, G. ( 1986). Heteroduplex stabilities in highly repetitive DNA. An hypothesis for the polymorphism of Plasmodium parasite antigenic response. Federation of the European Biochemical Societies Letters 197, 5–8.CrossRefGoogle Scholar
Dodin, G., Vandergheynst, P., Levoir, P, Cordier, C. and Marcourt, L. ( 2000). Fourier and wavelet transform analysis, a tool for visualizing regular patterns in DNA sequences. Journal of Theoretical Biology 206, 323–326.CrossRefGoogle Scholar
Dover, G. A. ( 1995). Slippery DNA runs on and on and on …. Nature Genetics 10, 254–256.CrossRefGoogle Scholar
Frevert, U. ( 2004). Sneaking in through the back entrance: the biology of malaria liver stages. Trends in Parasitology 20, 417–424.CrossRefGoogle Scholar
Gamain, B., Miller, L. H. and Baruch, D. ( 2001). The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes. Proceedings of the National Academy of Sciences, USA 98, 2664–2669.CrossRefGoogle Scholar
Gardner, M. J., Tettelin, H., Carucci, D. J., Cummings, L. M., Aravind, L., Koonin, E. V., Shallom, S., Mason, T., Yu, K., Fujii, C., Pederson, J., Shen, K., Jing, J., Aston, C., Lai, Z., Schwartz, D. C., Pertea, M., Salberg, S., Zhou, L., Sutton, G. G., Clayton, R., White, O., Smith, H. O., Fraser, C. M., Adams, M. D., Venter, J. C. and Hoffman, S. L. ( 1998). Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum Science 282, 1126–1132.Google Scholar
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., Paulsen, I. T., James, K., Eisen, J. A., Rutherford, K., Salzberg, S. L., Craig, A., Kyes, S., Chan, M., Nene, V., Shallom, S., Suh, B., Peterson, J., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., Haft, D., Mather, M. W., Vaidya, A. B., Martin, D. M. A., Fairlamb, A. H., Fraunholz, M. J., Roos, D. S., Ralph, S. A., McFadden, G. I., Cummings, L. M., Subramanian, G. M., Mungall, C., Venter, J. C., Carucci, D. J., Hoffman, S. L., Newbold, C., Davis, R. W., Fraser, C. M. and Barrell, B. ( 2002 a). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, London 419, 498–511.Google Scholar
Gardner, M. J., Shallom, S., Carlton, J. M., Salzberg, S. L., Nene, V., Shoaibi, A., Ciecko, A., Lynn, J., Rizzo, M., Weaver, B., Jarrahi, B., Brenner, M., Parvizi, B., Tallon, L., Moazzez, A., Granger, D., Fujii, C., Hansen, C., Pederson, J., Feldblyum, T., Peterson, J., Suh, B., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., White, O., Cummings, L. M., Smiyh, H. O., Adams, M. D., Venter, J. C., Carucci, D. J., Hoffman, S. L. and Fraser, C. M. ( 2002 b). Sequence of Plasmodium falciparum chromosomes 2,10, 11 and 14. Nature, London 419, 531–534.Google Scholar
Gravenor, M. B. and Lloyd, A. L. ( 1998). Reply to: Models for the in-host dynamics of malaria revisited: errors in some basic models lead to large over-estimates of growth rates. Parasitology 117, 409–410.CrossRefGoogle Scholar
Hall, N., Pain, A., Berriman, M., Churcher, C., Harris, B., Mungall, K., Bowman, S., Atkin, R., Baker, S., Barron, A., Brooks, K., Buckee, C. O., Burrows, C., Cherevach, I., Chillingworth, C., Chillingworth, T., Christodoulou, Z., Clark, L., Clark, R., Corton, C., Cronin, A., Davies, R., Davis, P., Dear, P., Dearden, F., Doggett, J., Feltwell, T., Goble, A., Goodhead, I., Gwilliam, R., Hamlin, N., Hance, Z., Harper, D., Hauser, H., Hornsby, T., Holroyd, S., Horrocks, P., Humphray, S., Jagels, K., James, K. D., Johnson, D., Kerhornou, A., Knights, A., Konfortov, B., Kyes, S., Larke, N., Lawson, D., Lennard, N., Line, A., Maddison, M., McLean, J., Mooney, P., Moule, S., Murphy, L., Oliver, K., Ormond, D., Price, C., Quail, M. A., Rabbinowitsch, E., Rajandream, M., Rutter, S., Rutherford, K. M., Sanders, M., Simmonds, M., Seeger, K., Sharp, S., Smith, R., Sqares, R., Squares, S., Stevens, K., Taylor, K., Tivey, A., Unwin, L., Whitehead, S., Woodward, J., Sulston, J. E., Craig, A., Newbold, C. and Barrell, B. G. ( 2002). Sequence of Plasmodium falciparum chromosomes 1,3–9 and 13. Nature, London 419, 527–531.CrossRefGoogle Scholar
Levinson, G. and Gutman, G. A. ( 1987). Slipped strand mispairing: a major mechanism for DNA sequence evolution. Molecular Biology of Evolution 4, 203–221.Google Scholar
Margos, G., Bannister, L. H., Dlukevsky, A. R., Hopkins, J., Williams, I. T. and Mitchell, G. H. ( 2004). Correlation of structural development and differential expression of invasion-related molecules in schizonts of Plasmodium falciparum. Parasitology 129, 273–286.CrossRefGoogle Scholar
Molineaux, L., Diebner, H. H., Eichner, M., Collins, W. E., Jeffery, G. M. and Dietz, K. ( 2001). Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology 122, 379–391.CrossRefGoogle Scholar
Paget-McNicol, S., Gatton, M., Hastings, I. and Saul, A. ( 2002). The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling. Parasitology 124, 225–235.CrossRefGoogle Scholar
Recker, M., Nee, S., Bull, P. C., Kinyanjul, S., Marsh, K., Newbold, C. and Gupta, S. ( 2004). Transient cross-reactive immune response can orchestrate antigenic variation in malaria. Nature, London 429, 555–558.CrossRefGoogle Scholar
Saul, A. ( 1998). Models for the in-host dynamics of malaria revisited: errors in some basic models lead to large over-estimates of growth rates. Parasitology 117, 405–407.CrossRefGoogle Scholar
Saveliev, A., Everett, C., Sharpe, T., Webster, Z. and Festenstein, R. ( 2003). DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature, London 422, 909–913.CrossRefGoogle Scholar
Scherf, A., Figueiredo, L. M. and Freitas-Junior, L. H. ( 2001). Plasmodium telomeres: a pathogen's perspective. Current Opinion in Microbiology 4, 409–414.CrossRefGoogle Scholar
Sinden, R. S. ( 2001). Origins of instability. Nature, London 411, 757–758.CrossRefGoogle Scholar
Smith, T., Dietz, K., Vounatsou, P., Müller, I., English, M. and Marsh, K. ( 2004). Bayesian age-stage modelling of Plasmodium falciparum sequestered parasitic loads in severe malaria patients. Parasitology 129, 289–299.CrossRefGoogle Scholar
Taylor, H. M., Kyes, S., Harris, D., Kriek, N. and Newbold, C. ( 2000). A study of var gene transcription in vitro using universal var gene primers. Molecular and Biochemical Parasitology 105, 13–33.CrossRefGoogle Scholar
Tongren, J. E., Zavala, F., Roos, D. S. and Riley, E. M. ( 2004). Malaria vaccines: if at first you don't succeed …. Trends in Parasitology 20, 604–610.CrossRefGoogle Scholar
Tsuji, M. and Zavala, F. ( 2003). T cells as mediators of protective immunity against liver stages of Plasmodium. Trends in Parasitology 19, 88–93.CrossRefGoogle Scholar
Wan, H. and Wootton, J. C. ( 2000). A global compositional complexity measure for biological sequences: AT-rich and GC-rich genomes encode less complex proteins. Computers and Chemistry 24, 71–94.CrossRefGoogle Scholar
Wootton, J. C. ( 1994). Non-globular domains in protein sequences: automated segmentation using complexity measures. Computers and Chemistry 18, 269–285.CrossRefGoogle Scholar