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ParasitesMolecular Biology,

Drug and Vaccine Design

Proceedings of a UCLA Symposium, Held at Keystone, Colorado,April 3-10, 1989

Editors

Nina ArabianIntercampus Program.in Molecular Parasitology

University.of California jBerkeley and San Francisco, California

Anthony CeramiLaboratory of Medical Biochemistry

The Rockefeller UniversityNew York, New York

®WILEY-LISSA JOHN WILEY & SONS, INC., PUBLICATION

New York • Chichester • Brisbane • Toronto • Singapore

Contents

Contributors jd

PrefaceNina Agabian and Anthony Cerami xxi

I. GENE EXPRESSION DURING PARASITE DIFFERENTIATION ANDDEVELOPMENTA. Regulation During Development and Differentiation

Trypanosoma cruzi as a Model System for Studying Cell DifferentiationSamuel Goldenberg 1

The Rodent Malaria Parasite Plasmodium berghei as a Modelsystem forthe Study of Gene Expression During Gametocytogenesis

Alex van Belkum, Leen-Jan van Doom, Andy Waters, ThomasMcCutchan, Chris Janse, Barend Mons, and Huub Schellekens 7

A Developmental^ Regulated, Cyclic-AMP Inducible Gene Expressedby Metacyclic Trypomastigotes of Trypanosoma cruzi

Stephen Heath, Kenneth Vernick, Sara Hieny, and Alan Sher 27A Developmental^ Regulated Gene of Leishmania major ShowsHomology to Superfamily of Reductase Genes

Terry W. Spithill, Getachew Z. Kidane, John M. Pettitt, Peter J. Murray,Theresa A. Glaser, and Nicholas Samaras 35

myc-Homologues in Trypanosoma bruceiChoong H. Kim, M.E.M. Colmerauer, D.G. Guiney, and Charles E.Davis j . . . 49

B. Regulation of VSG Gene Expression in African Trypanosomes

Control of Variant-Specific Surface Glycoprotein Expression Sites inTrypanosoma brucei

P. Borst, J. Zomerdijk, M. Ouellette, M. Crozatier, and A. Ten Asbroek. 59Structure and Expression of Trypanosome Metacyclic VSG ExpressionSites

Keith R. Matthews, Paul Shiels, Sheila V. Graham, and J. David Barry. 73Two Metacyclic VSG Gene Expression Sites of Trypanosoma bruceigambiense

Debra A. Barnes and Nina Agabian 87

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Ribonuclease Protection Determines Sequences Specific to a SingleVariable Surface Glycoprotein Gene Expression Site

Andrew W. Stadnyk, John K. Scholler, Peter J. Myler, and Kenneth D.Stuart 99

C. Transcriptional Signals and RNA Processing

The Implications of Selective and Extensive RNA EditingKenneth Stuart, Donna J. Koslowsky, G. Jayarama Bhat, and Jean E.Feagin I l l

Transcriptional Analysis of the Major Merozoite Surface AntigenPrecursor (gpl95) Gene of Plasmodium falciparum

Peter J. Myler 123

n. THE POTENTIAL FOR MOLECULAR GENETICS IN PARASITESYSTEMSDNA-Mediated Transfection of the Trypanosomatid ProtozoanLeptomonas seymouri

Vivian Bellofatto, David R. Sherman, and George A.M. Cross 139Transfection of Leishmania enriettii and Expression of ChloramphenicolAcetyl Transferase Gene

Avraham Laban and Dyann F. Wirth 149A New Giardia lamblia Virus-Related RNA in the Extracts of InfectedCells

Eric S. Furfine, Alice L. Wang, and C.C. Wang 159Discussion Summary: DNA Transformation- Protozoa

Barbara Sollner-Webb and Alice Wang 169-

HI. MOLECULES OF THE PARASITE MEMBRANEStructure of the Leishmania donovani Lipophosphoglycan

S.J. Turco 173Molecular Genetics of Repetitive Antigens and the Major SurfaceGlycoprotein of Leishmania '

W. Robert McMaster, Linda L. Button, Anne E. Wallis, Tom Frommel,John Webb, Yoshihisa Fujikura, and Neil E. Reiner 183

Multiple Distinct gp63-Like Genes in Amastigotes of Leishmaniadonovani

R.D.C. Maingon, L. Elson, M. Hommel, J.M. Crampton, and M.L.Chance 191

Cloning of Two Trypomastigote-Specific Surface Antigen Genes FromTrypanosoma cruzi

Garry B. Takle, Alison J. Young, and L. Hudson 205Identification of an EGF Receptor Homologue in Trypanosomes

Geoff Hide, Alex Gray, Catherine M. Harrison, and Andrew Tait 213

Contents ix

A 60 kDA Plasmodium falciparum Protein at the Moving JunctionFormed Between Merozoite and Erythrocyte During Invasion: Analysisby Two-Color Immunofluorescence

Francis W. Klotz and Louis H. Miller 225

IV. MOLECULAR MODELING AND PARASITE DRUG DESIGNA. Enzymes in Parasite Systems

Unique Properties of Glycosomal EnzymesFred R. Opperdoes, Rik K. Wierenga, Martin E.M. Noble, Wim G.J.Hoi, Michele Willson, Douglas A. Kuntz, Mia Callens, andJacques Perie 233

Glycosomal Biogenesis and Glucose Transport in Trypanosoma bruceiMarilyn Parsons, Keith Alexander, Teresa Hill, Barbara Nielsen, HarryF. Dovey, and C.C. Wang 247

TrypanothioneNicholas J. Murgolo, Anthony Cerami, and Graeme B. Henderson 263

The DNA-Dependent RNA Polymerases of Trypanosoma bruceiErnst J.M Grondal, Raymond Evers, Josef Kock, Waldemar Jess, andAlbert W.C.A. Cornelissen 279

Peptidases of Trypanosoma cruziCatherine M. Lowndes, Niamh Healy, Stephen Greig, and Frank Ashall. 297

B. Drug Resistance

Molecular Mechanisms of Drug Resistance in PlasmodiumAlan F. Cowman, Simon J. Foote, Andrew M. Lew, and Denise Galatis. 311

The Multidrug Resistance Gene of P. falciparum; Does it MediateChloroquine Resistance

Simon J. Foote, Jennifer K. Thompson, Vikki Marshall, Alan F.Cowman, Beverly A. Biggs, Graham V. Brown, and David J. Kemp. . . . 325

Amplification of a Gene Related to Mammalian MDR Genes in Drug-Resistant Plasmodium falciparum

Dyann F. Wirth, Craig Wilson, Adelfa E. Serrano, Annemarie Wasley,Michael Bogenschutz, and Anuraj H. Shankar 335

V. VACCINESVaccines and Vaccination Strategies: Helminths

Graham F. Mitchell 349Chlamydia Trachomatis Antigens in Immunity and Pathogenesis

Richard S. Stephens, Elizabeth A. Wagar, Judith E. Allen, and PatrikBavoil 365

Heterogeneity in the Plasmodium falciparum Circumsporozoite ProteinGene and Its Implications for Vaccine Development

Michael J. Lockyer, Kevin Marsh, and Christopher I. Newbold 379

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Schistosoma mansoni p-37 Antigen: Identification by Antibodies FromResistant Subjects and Molecular Cloning

V. Goudot-Crozel, P. Rihet, C. Demeure, P. Couissinier, A. Prata, andA.J. Dessein 391

VI. CYTOKINES IN PARASITIC DISEASEReview: Cachectin/TNF in the Cachexia of Infection

Kevin J. Tracey and Anthony Cerami 401Cytokine Production and Function During Murine Leishmaniasis

Frederick P. Heinzel, Michael D. Sadick, Bettie J. Holaday, Rogelio S.Dawkins, Robert T. Pu, and Richard M. Locksley 411

TNF: An Essential Mediator in Cerebral Malaria?Georges E. Grau, Pierre-Francois Piguet, Pierre Vassalli, and Paul-HenriLambert 427

Identification of Putatively Protective Antigens of Brugia malayi byTheir Ability to Stimulate Spleen Cells of Immune Mice to ProduceIL-3 In Vitro

Neil Storey and Mario Philipp 441Discussion Summary: Cytokines in Parasitic Disease

Richard M. Locksley 451

VH. PATHOGENESIS AND VIRULENCE FACTORS: SESSION SUMMARYDiscussion Session: Pathogenesis and Virulence Factors

David Mirelman 455

Vffl. EPIDEMIOLOGYMolecular Karyotype Analysis of Leishmania brazUiensis panamensisFrom the Pacific Coast Region of Colombia

S.H. Giannini and N.G. Saravia 465Field Testing of Monoclonal Probe Specific for Infective Larvae ofHuman Brugian Parasites

Clotilde K.S. Carlow, Alexandra Suwita, Z. Bahang, Purnomo, F.Partono, and Mario Philipp :•. 479

Index 489