Exome and Transcriptome Sequencing of Identifies a Locus That Confers Resistance to and Alters the Immune Response
Within mosquito populations, genetic differences between individuals affect their ability to transmit human diseases such as malaria, dengue fever, and lymphatic filariasis. In the mosquito Aedes aegypti, some individuals are genetically resistant to Brugia malayi, a mosquito-vectored parasite that causes a debilitating tropical disease called lymphatic filariasis. To characterize the genetic basis of resistance, we identified resistant and susceptible mosquitoes from a wild Kenyan population, and sequenced the protein-coding region of their genomes (the exome). This allowed us to locate a single region of the mosquito genome that is causing resistance and to identify genes that may be controlling the trait. To understand the mechanisms of resistance, we measured gene expression. The susceptible mosquitoes have reduced expression of immunity genes after they are infected with B. malayi, including genes known to kill this group of parasites. This is possibly because their immune response is being suppressed by the parasites. We conclude that resistance is controlled by a single locus and show that resistance results in an increased immune response.
Vyšlo v časopise:
Exome and Transcriptome Sequencing of Identifies a Locus That Confers Resistance to and Alters the Immune Response. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004765
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004765
Souhrn
Within mosquito populations, genetic differences between individuals affect their ability to transmit human diseases such as malaria, dengue fever, and lymphatic filariasis. In the mosquito Aedes aegypti, some individuals are genetically resistant to Brugia malayi, a mosquito-vectored parasite that causes a debilitating tropical disease called lymphatic filariasis. To characterize the genetic basis of resistance, we identified resistant and susceptible mosquitoes from a wild Kenyan population, and sequenced the protein-coding region of their genomes (the exome). This allowed us to locate a single region of the mosquito genome that is causing resistance and to identify genes that may be controlling the trait. To understand the mechanisms of resistance, we measured gene expression. The susceptible mosquitoes have reduced expression of immunity genes after they are infected with B. malayi, including genes known to kill this group of parasites. This is possibly because their immune response is being suppressed by the parasites. We conclude that resistance is controlled by a single locus and show that resistance results in an increased immune response.
Zdroje
1. Lefèvre T, Vantaux A, Dabiré KR, Mouline K, Cohuet A. Non-genetic determinants of mosquito competence for malaria parasites. PLoS Pathog. 2013;9: e1003365. doi: 10.1371/journal.ppat.1003365 23818841
2. Beerntsen BT, James AA, Christensen BM. Genetics of mosquito vector competence. Microbiol Mol Biol Rev. 2000;64: 115–137. 10704476
3. Riehle MM, Markianos K, Niaré O, Xu J, Li J, Touré AM, et al. Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region. Science. 2006;312: 577–9. 16645095
4. Collins FH, Sakai RK, Vernick KD, Paskewitz S, Seeley DC, Miller LH, et al. Genetic selection of a Plasmodium-refractory strain of the malaria vector Anopheles gambiae. Science. 1986;234: 607–610. 3532325
5. Macdonald WW. The selection of a strain of Aedes aegypti susceptible to infection with semi-periodic Brugia malayi. Ann Trop Med Parasitol. 1962;56: 368–372.
6. Bosio CF, Fulton RE, Salasek ML, Beaty BJ, Black WC IV. Quantitative trait loci that control vector competence for dengue-2 virus in the mosquito Aedes aegypti. Genetics. 2000;156: 687–698. 11014816
7. Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. 2011;476: 454–7. doi: 10.1038/nature10356 21866160
8. Taylor MJ, Hoerauf A, Bockarie M. Lymphatic filariasis and onchocerciasis. Lancet. 2010;376: 1175–85. doi: 10.1016/S0140-6736(10)60586-7 20739055
9. Bockarie MJ, Pedersen EM, White GB, Michael E. Role of vector control in the global program to eliminate lymphatic filariasis. Annu Rev Entomol. 2009;54: 469–87. doi: 10.1146/annurev.ento.54.110807.090626 18798707
10. Dissanaike AS. Zoonotic aspects of filarial infections in man. Bull World Health Organ. 1979;57: 349–57. 314349
11. Erickson SM, Xi Z, Mayhew GF, Ramirez JL, Aliota MT, Christensen BM, et al. Mosquito infection responses to developing filarial worms. PLoS Negl Trop Dis. 2009;3: e529. doi: 10.1371/journal.pntd.0000529 19823571
12. Macdonald WW. The genetic basis of susceptibility to infection with semi-periodic Brugia malayi to Aedes aegypti. Ann Trop Med Parasitol. 1962;56: 373–382.
13. Kobayashi M, Ogura N, Yamamoto H. Studies on filariasis VIII: Histological observation on the abortive development of Brugia malayi larvae in the thoracic muscles of the mosquitoes, Armigeres subalbatus. Jpn J Santi Zool. 1986;37: 127–132.
14. Aliota MT, Fuchs JF, Mayhew GF, Chen C-C, Christensen BM. Mosquito transcriptome changes and filarial worm resistance in Armigeres subalbatus. BMC Genomics. 2007;8: 463. 18088420
15. Paige C, Craig G Jr. Variation in filarial susceptibility among east African populations of Aedes aegypti. J Med Entomol. 1975;12: 485–493. 1223294
16. Macdonald WW, Ramachandran CP. The influence of the gene fm (filarial susceptibility, Brugia malayi) on the susceptibility of Aedes aegypti to seven strains of Brugia, Wuchereria and Dirofilaria. Ann Trop Med Parasitol. 1965;59: 64–73. 14297358
17. Macdonald WW, Sheppard PM. Cross-over values in the sex chromosomes of the mosquito Aedes aegypti and evidence for the presence of inversions. Ann Trop Med Parasitol. 1965; 74–87.
18. Severson DW, Mori A, Zhang Y, Christensen BM. Chromosomal mapping of two loci affecting filarial worm susceptibility in Aedes aegypti. Insect Mol Biol. 1994;3: 67–72. 7987523
19. Juneja P, Osei-Poku J, Ho YS, Ariani C V, Palmer WJ, Pain A, et al. Assembly of the genome of the disease vector Aedes aegypti onto a genetic linkage map allows mapping of genes affecting disease transmission. PLoS Negl Trop Dis. 2014;8: e2652. doi: 10.1371/journal.pntd.0002652 24498447
20. Lowenberger CA, Ferdig MT, Bulet P, Khalili S, Hoffmann J a, Christensen BM. Aedes aegypti: induced antibacterial proteins reduce the establishment and development of Brugia malayi. Exp Parasitol. 1996;83: 191–201. doi: 10.1006/expr.1996.0066 8682188
21. Kambris Z, Cook PE, Phuc HK, Sinkins SP. Immune activation by life-shortening Wolbachia and reduced filarial competence in mosquitoes. Science. 2009;326: 134–6. doi: 10.1126/science.1177531 19797660
22. Chalk R, Townson H, Ham P. Brugia panhangi: The effects of cecropins on microfilariae in vitro and in Aedes aegypti. Exp Parasitol. 1995;80: 401–406. 7729475
23. Stathopoulos S, Neafsey DE, Lawniczak MKN, Muskavitch MAT, Christophides GK. Genetic dissection of Anopheles gambiae gut epithelial responses to Serratia marcescens. PLoS Pathog. 2014;10: e1003897. doi: 10.1371/journal.ppat.1003897 24603764
24. Weetman D, Wilding CS, Steen K, Morgan JC, Simard F, Donnelly MJ. Association mapping of insecticide resistance in wild Anopheles gambiae populations: major variants identified in a low-linkage disequilbrium genome. PLoS One. 2010;5: e13140. doi: 10.1371/journal.pone.0013140 20976111
25. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson D a, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011;12: 745–55. doi: 10.1038/nrg3031 21946919
26. Osei-Poku J. The evolution and genetics of vector competence in mosquito disease vectors. Ph. D Thesis, The University of Cambridge. Available: https://www.repository.cam.ac.uk/bitstream/handle/1810/245011/Osei-PokuPhD%20thesis.pdf. 2012. p. 226.
27. Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, et al. Genome sequence of Aedes aegypti, a major arbovirus vector. Science. 2007;316: 1718–23. 17510324
28. Lohse M, Bolger AM, Nagel A, Fernie AR, Lunn JE, Stitt M, et al. RobiNA: a user-friendly, integrated software solution for RNA-Seq-based transcriptomics. Nucleic Acids Res. 2012;40: W622–7. doi: 10.1093/nar/gks540 22684630
29. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25: 1754–60. doi: 10.1093/bioinformatics/btp324 19451168
30. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25: 2078–9. doi: 10.1093/bioinformatics/btp352 19505943
31. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20: 1297–1303. doi: 10.1101/gr.107524.110 20644199
32. Skotte L, Korneliussen TS, Albrechtsen A. Association testing for next-generation sequencing data using score statistics. Genet Epidemiol. 2012;36: 430–7. doi: 10.1002/gepi.21636 22570057
33. Korneliussen TS, Albrechtsen A, Nielsen R. ANGSD: Analysis of Next Generation Sequencing Data. BMC Bioinformatics. 2014;15: 356. 25420514
34. Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27: 2987–93. doi: 10.1093/bioinformatics/btr509 21903627
35. Kim SY, Lohmueller KE, Albrechtsen A, Li Y, Korneliussen T, Tian G, et al. Estimation of allele frequency and association mapping using next-generation sequencing data. BMC Bioinformatics. BioMed Central Ltd; 2011;12: 231. doi: 10.1186/1471-2105-12-231 21663684
36. McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics. 2010;26: 2069–70. doi: 10.1093/bioinformatics/btq330 20562413
37. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9: 357–9. doi: 10.1038/nmeth.1923 22388286
38. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. BioMed Central Ltd; 2013;14: R36. doi: 10.1186/gb-2013-14-4-r36 23618408
39. Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, Crabtree J, et al. Draft genome of the filarial nematode parasite Brugia malayi. Science. 2007;317: 1756–60. 17885136
40. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26: 139–40. doi: 10.1093/bioinformatics/btp616 19910308
41. Anders S, McCarthy DJ, Chen Y, Okoniewski M, Smyth GK, Huber W, et al. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor. Nat Protoc. 2013;8: 1765–86. doi: 10.1038/nprot.2013.099 23975260
42. Kofler R, Pandey RV, Schlötterer C. PoPoolation2: identifying differentiation between populations using sequencing of pooled DNA samples (Pool-Seq). Bioinformatics. 2011;27: 3435–6. doi: 10.1093/bioinformatics/btr589 22025480
43. Zou Z, Souza-Neto J, Xi Z, Kokoza V, Shin SW, Dimopoulos G, et al. Transcriptome analysis of Aedes aegypti transgenic mosquitoes with altered immunity. PLoS Pathog. 2011;7: e1002394. doi: 10.1371/journal.ppat.1002394 22114564
44. Souza-Neto JA, Sim S, Dimopoulos G. An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci U S A. 2009;106: 17841–6. doi: 10.1073/pnas.0905006106 19805194
45. Rancès E, Ye YH, Woolfit M, McGraw E a, O’Neill SL. The relative importance of innate immune priming in Wolbachia-mediated dengue interference. PLoS Pathog. 2012;8: e1002548. doi: 10.1371/journal.ppat.1002548 22383881
46. Lawson D, Arensburger P, Atkinson P, Besansky NJ, Bruggner R V, Butler R, et al. VectorBase: a data resource for invertebrate vector genomics. Nucleic Acids Res. 2009;37: D583–7. doi: 10.1093/nar/gkn857 19028744
47. Timoshevskiy VA, Kinney NA, DeBruyn BS, Mao C, Tu Z, Severson DW, et al. Genomic composition and evolution of Aedes aegypti chromosomes revealed by the analysis of physically mapped supercontigs. BMC Biol. 2014;12: 27. doi: 10.1186/1741-7007-12-27 24731704
48. Timoshevskiy VA, Severson DW, Debruyn BS, Black WC, Sharakhov I V, Sharakhova M V. An integrated linkage, chromosome, and genome map for the yellow fever mosquito Aedes aegypti. PLoS Negl Trop Dis. 2013;7: e2052. doi: 10.1371/journal.pntd.0002052 23459230
49. Ramachandran CP. Biological aspects in the transmission of Brugia malayi by Aedes aegypti in the laboratory. J Med Entomol. 1966;3: 239–252. 4964879
50. Dissanayake SN, Ribeiro JM, Wang M-H, Dunn WA, Yan G, James AA, et al. aeGEPUCI: a database of gene expression in the dengue vector mosquito, Aedes aegypti. BMC Res Notes. 2010;3: 248. doi: 10.1186/1756-0500-3-248 20920356
51. Choi Y-J, Aliota MT, Mayhew GF, Erickson SM, Christensen BM. Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions. PLoS Negl Trop Dis. 2014;8: e2905. doi: 10.1371/journal.pntd.0002905 24853112
52. Rodriguez PH, Torres C, Marotta JA. Comparative development of Brugia malayi in susceptible and refractory genotypes of Aedes aegypti. J Parasitol. 1984;70: 1001–2. 6527177
53. Zou Z, Shin SW, Alvarez KS, Kokoza V, Raikhel AS. Distinct melanization pathways in the mosquito Aedes aegypti. Immunity. Elsevier Ltd; 2010;32: 41–53. doi: 10.1016/j.immuni.2009.11.011 20152169
54. Choi Y-J, Fuchs JF, Mayhew GF, Yu HE, Christensen BM. Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection. Insect Biochem Mol Biol. Elsevier Ltd; 2012;42: 729–38. doi: 10.1016/j.ibmb.2012.06.005 22796331
55. Roy SG, Raikhel AS. Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E-BP) in the mosquito Aedes aegypti. FASEB J. 2012;26: 1334–42. doi: 10.1096/fj.11-189969 22159149
56. Borovsky D. Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control. J Exp Biol. 2003;206: 3869–3875. 14506222
57. Brackney DE, Isoe J, Black WC IV, Zamora J, Foy BD, Miesfeld RL, et al. Expression profiling and comparative analyses of seven midgut serine proteases from the yellow fever mosquito, Aedes aegypti. J Insect Physiol. Elsevier Ltd; 2010;56: 736–44. doi: 10.1016/j.jinsphys.2010.01.003 20100490
58. Bonizzoni M, Dunn WA, Campbell CL, Olson KE, Dimon MT, Marinotti O, et al. RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti. BMC Genomics. 2011;12: 82. doi: 10.1186/1471-2164-12-82 21276245
59. Randall TA, Perera L, London RE, Mueller GA. Genomic, RNAseq, and molecular modeling evidence suggests that the major allergen domain in insects evolved from a homodimeric origin. Genome Biol Evol. 2013;5: 2344–58. doi: 10.1093/gbe/evt182 24253356
60. Bandi C, Anderson TJC, Genchi C, Blaxter ML, Celoria V. Phylogeny of Wolbachia in filarial nematodes. Proc R Soc B Biol Sci. 1998;265: 2407–2413. 9921679
61. Jupatanakul N, Sim S, Dimopoulos G. Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue virus infection. Dev Comp Immunol. Elsevier Ltd; 2014;43: 1–9. doi: 10.1016/j.dci.2013.10.002 24135719
62. Shin SW, Bian G, Raikhel AS. A Toll receptor and a cytokine, Toll5A and Spz1C, are involved in toll antifungal immune signaling in the mosquito Aedes aegypti. J Biol Chem. 2006;281: 39388–95. 17068331
63. Mackay TFC, Stone EA, Ayroles JF. The genetics of quantitative traits: challenges and prospects. Nat Rev Genet. 2009;10: 565–77. doi: 10.1038/nrg2612 19584810
64. Wilfert L, Schmid-Hempel P. The genetic architecture of susceptibility to parasites. BMC Evol Biol. 2008;8: 187. doi: 10.1186/1471-2148-8-187 18590517
65. Schwartz A, Koella JC. Melanization of Plasmodium falciparum and C-25 Sephadex beads by field-caught Anopheles gambiae (Diptera: Culicidae) from southern Tanzania. J Med Entomol. 2002;39: 84–88. 11931276
66. Macdonald SJ, Long AD. A potential regulatory polymorphism upstream of hairy is not associated with bristle number variation in wild-caught Drosophila. Genetics. 2004;167: 2127–31. 15342546
67. Magwire MM, Fabian DK, Schweyen H, Cao C, Longdon B, Bayer F, et al. Genome-wide association studies reveal a simple genetic basis of resistance to naturally coevolving viruses in Drosophila melanogaster. PLoS Genet. 2012;8: e1003057. doi: 10.1371/journal.pgen.1003057 23166512
68. Poirie M, Frey F, Hita M, Huguet E, Lemeunier F, Periquet G, et al. Drosophila resistance genes to parasitoids: chromosomal location and linkage analysis. Proc R Soc B Biol Sci. 2000;267: 1417–1421. 10983825
69. Orr HA, Shannon I. The genetics of adaptation: the genetic basis of resistance to wasp parasitism in Drosophila melanogaster. Am Nat. Society for the Study of Evolution; 1997;51: 1877–1885.
70. Hill AVS. Evolution, revolution and heresy in the genetics of infectious disease susceptibility. Philos Trans R Soc B Biol Sci. 2012;367: 840–849. doi: 10.1098/rstb.2011.0275 22312051
71. Rodriguez P, Craig G Jr. Susceptibility to Brugia pahangi in geographic strains of Aedes aegypti. Am J Trop Med Hygeine. 1973;22: 53–61. 4684889
72. Terwedow HA, Craig GB. Infection of female and male Aedes aegypti (Diptera: Culicidae) with the filarial parasite Waltonella flexicauda. J Med Entomol. 1977;14: 421–424. 305482
73. Sulaiman I, Townson H. The genetic basis of susceptibility to infection with Dirofilaria immitis in Aedes aegypti. Ann Trop Med Parasitol. 1980;74: 635–646. 7458468
74. Mackay TFC, Richards S, Stone EA, Barbadilla A, Ayroles JF, Zhu D, et al. The Drosophila melanogaster Genetic Reference Panel. Nature. 2012;482: 173–8. doi: 10.1038/nature10811 22318601
75. Waterhouse RM, Kriventseva E V, Meister S, Xi Z, Alvarez KS, Bartholomay LC, et al. Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science. 2007;316: 1738–43. doi: 10.1126/science.1139862 17588928
76. Turner JD, Langley RS, Johnston KL, Gentil K, Ford L, Wu B, et al. Wolbachia lipoprotein stimulates innate and adaptive immunity through Toll-like receptors 2 and 6 to induce disease manifestations of filariasis. J Biol Chem. 2009;284: 22364–78. doi: 10.1074/jbc.M901528200 19458089
77. Kokoza V, Ahmed A, Woon Shin S, Okafor N, Zou Z, Raikhel AS. Blocking of Plasmodium transmission by cooperative action of Cecropin A and Defensin A in transgenic Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A. 2010;107: 8111–6. doi: 10.1073/pnas.1003056107 20385844
78. Castillo JC, Reynolds SE, Eleftherianos I. Insect immune responses to nematode parasites. Trends Parasitol. Elsevier Ltd; 2011;27: 537–47. doi: 10.1016/j.pt.2011.09.001 21982477
79. Christensen BM, Lafond MM. Parasite-induced suppression of the immune response in Aedes aegypti to Brugia pahangi. J Parasitol. 1986;72: 216–219. 3734990
80. Hansen IA, Attardo GM, Park J-H, Peng Q, Raikhel AS. Target of rapamycin-mediated amino acid signaling in mosquito anautogeny. Proc Natl Acad Sci U S A. 2004;101: 10626–31. 15229322
81. Evans AM, Aimanova KG, Gill SS. Characterization of a blood-meal-responsive proton-dependent amino acid transporter in the disease vector, Aedes aegypti. J Exp Biol. 2009;212: 3263–71. doi: 10.1242/jeb.029553 19801431
82. Hurd H, Hogg JC, Renshaw M. Interactions between bloodfeeding, fecundity and infection in mosquitoes. Parasitol Today. 1995;11: 411–416.
83. Caragata EP, Rancès E, O’Neill SL, McGraw EA. Competition for amino acids between Wolbachia and the mosquito host, Aedes aegypti. Microb Ecol. 2014;67: 205–18. doi: 10.1007/s00248-013-0339-4 24337107
84. Sylvestre G, Gandini M, Maciel-de-Freitas R. Age-dependent effects of oral infection with dengue virus on Aedes aegypti (Diptera: Culicidae) feeding behavior, survival, oviposition success and fecundity. PLoS One. 2013;8: e59933. doi: 10.1371/journal.pone.0059933 23555838
85. Ferdig MT, Beerntsen BT, Spray FJ, Li J, Christensen BM. Reproductive costs associated with resistance in a mosquito-filarial worm system. Am J Trop Med Hygeine. 1993;49: 756–762. 7904130
86. Gaaboub A. Observations on the basal follicle numbers developed per female of two strains of Aedes aegypti after being fed on hosts with different levels of microfilariae of Brugia pahangi. J Invertebr Pathol. 1976;28: 203–207. 965782
87. Javadian E, Macdonald WW. The effect of infection with Brugia pahangi and Dirofilaria repens on the egg-production of Aedes aegypti. Ann Trop Med Parasitol. 1974;68: 477–81. 4480018
88. Rono MK, Whitten MMA, Oulad-Abdelghani M, Levashina EA, Marois E. The major yolk protein vitellogenin interferes with the anti-plasmodium response in the malaria mosquito Anopheles gambiae. PLoS Biol. 2010;8: e1000434. doi: 10.1371/journal.pbio.1000434 20652016
89. Brackney DE, Foy BD, Olson KE. The effects of midgut serine proteases on dengue virus type 2 infectivity of Aedes aegypti. Am J Trop Med Hyg. 2008;79: 267–74. 18689635
90. Molina-Cruz A, Gupta L, Richardson J, Bennett K, Black W IV, Barillas-Mury C. Effect of mosquito midgut trypsin activity on dengue-2 virus infection and dissemination in Aedes aegypti. Am J Trop Med Hyg. 2005;72: 631–7. 15891140
91. Shahabudin M, Criscio M, Kaslow D. Unique specificity of in vitro inhibition of mosquito midgut trypsin-like activity correlates with in vivo inhibition of malaria parasite infectivity. Exp Parasitol. 1995;80: 212–219. 7534722
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