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Dissertation contains pages with print at a slant, filmed as received__________ 16. Other___________ _____ _____ _______________ University Microfilms international MECHANISMS OF IN VITRO PERSISTENCE OF TWD CANINE PARAMYXOVIRUSES AND IN VIVO NEUROPATHOGENICITY OF CANINE PARAINFLUENZA VIRUS Dissertation Presented in Partial Etilfillment of the Requiranents for The Degree Doctor of Philosophy in the Graduate School of the Ohio State IMiversity By Wolfgang K. BaumgSrtner, Dr. itied. vet. ***** The Ohio State University 1986 Dissertation Conmittee: Approved by Steven Krakcwka James R. Blakeslee Charles C. Capen Steven E. Vfeisbrode Adviser Department of Veterinary Pathobiology Copyright by Wolfgang K. Baumgârtnery Dr. med. vet. 1986 Dedication To nty vd-fe, Angelika, and iry son, Lars. 11 iOaSiCWLEDGayENTS The author wishes to ej^ress his sincerest appreciation to iry adviser. Dr. S. Krakcvto, for his guidance, encouraganents, enthus­ iasm, and patience during this project. I wish also to eatress iry gratitude to Dr. C. Capen, Chairman of the Department of Patho­ biology, for his encouragement and support for my second visit to The Ohio State University. The author would like to es^ress profound appreciation to Dr. J. Blakeslee and Dr. M. Axthelm for their collegiate support and advice. I thank Ms. S. Ringler, N.J. Austin and J. Dubena, vÆo most skillfully assisted me in ny in vitro and in vivo ejqjeriments. I would like to e3q>ress m y thanks to Ms. E. Handley and 0. Kindig for their technical assistance in preparing the electron- microscopic specimens. I thank Ms. V. Stump and R. I^an for their secretarial assis­ tance in -typing this dissertation. Last, but not least, I would like to express my appreciation and thanks to my colleague and friend. Dr. T. Rosol, for providing a constructive, competitive office environment. A final acknowledgement goes to The State of Ohio Canine Research fund grant 2 RDI NS-14821, NIH, PHS and the Deutschen Forschungsgemeinschaft for sipport of these studies. iii VITA July 20, 1952 ........................... B o m - Offenbach, West Germany 1 9 7 1 .................................. Abitur, Leibnizschule, Offenbach, West Germany 1978 .................................. Approbation, JLO-Giessen 1979-1981 .............................. Predoctoral fellow, DAAD, Department of Veterinary Pathobiology, The Ohio State University 198 1 .................................. Doktor med. vet.. Institute Vet. Path., Giessen 1982 .................................. Private practice 1983-1985 .............................. Postdoctoral fellow, DFG, Department of Veterinary Pathobiology, The Ohio State University 1986-Present ........................... Postdoctoral fellow, DFG, Institut für VeterinSr Pathologie der Justus Liebig Universitât, Giessen PUBLICATICNS Baumgârtner, W., Krakowka, S.: A Sirtple Method for the Histochemical Demonstration of Viral Inclusion Bodies in Cell îfonolayers in Micro­ titration Plate. Stain Technology (in press) 1986. Baumgârtner, W., Zajac, A., Hull, B.L., Andrews, F., Garry, F.: Paralaphostrongylosis in Llamas. J. Am. Vet. Med. Assoc. 187:1243- 1245, 1985. IV Baumgârtner, W. : Canine Parainfluenza Virus. In: Pathology of Viral Disease, R.G. Olsen, S. Krakoto, eds. CPC Press, Vol. II, Ch. 4, 1985. Baumgârtner, W., Posselt, H.J. : Kutane Altemariosis bei Hunden mit unspezifischen Dermatitiden. Kleintierpraxis 28:353-358, 1983. Baumgârtner, W., Posselt, H.J. : Ostrogeninduzierte hamorrhagische Diathese bei einer Hundin. Kleintierpraxis 27:419-420, 1982. Baumgârtner, W.K., Krakovdca, S., Kbestner, A., Evermann, J . : Ultra- structural Evaluation of Acute Encephalitis and Hydrocephalus in Dogs Caused by Canine Parainfluenza Virus. Vet. Pathol. 19:305-314, 1982. Baumgârtner, W.K., Krakcuflto, S., Kbestner, A., Evermann, J.: Acute Encephalitis and Hydrocephalus in Dogs Caused by Canine Parainfluenza Virus. Vet. Pathol. 19:79-92, 1982. Evermann, J., Krakowka, S., McKeiman, A.J., Baumgârtner, W.: In Vitro Identification and Characterization of a Virus Isolated from a Dog with Neurological Dysfunction. Infect. Irtittun. 31:1177-1183, 1981. Abstracts: Baumgârtner, W.K., Krakcudca, S., Koestner, A., Evermann, T.: Acute Encephalitis and Hydrocephalus in Dogs Caused by Canine Parainfluenza Virus. Annual Review of Hydrocephalus, 1983. S. Mabumoto, K. Satdheny, eds., Nevion Publishing Co., 1983, pp 7-8. FIELDS OF STUDY Major Field: Neuropathology, Ccmparatice Pathology, Pathogenesis of Viral Diseases TABLE OF CCNTENTS DEDICATIOSr................................................ ii ACKNCWLEDGEMENTS.......................................... iii VITA ...................................................... iv LIST OF T A B L E S .......................................... X LIST OF F I G U R E S ........................................ xii ABBREVIATICNS ............................................ xix CHAPTER Page I. A SIMPLE METHOD FOR THE HISTOCHEMICAL DEMONSTRATION OF VIRAL INCLUSION BODIES IN CRT.T. MONOLAYERS IN MICROTITRATION P L A T E S ........................... 3 Introduction ................................. 3 Materials and Methods ......................... 5 Results and Discussion ....................... 6 Summary ...................................... 8 R e f e r e n c e s ................................... 11 II. CANINE PARAINFLUENZA VIRUS: EVOLUTION OF TO VITRO PERSISTENCE AND PRffiUCTION OF INTERFERING VIRAL PARTICLES ...................................... 12 Introduction ................................. 12 Materials and Methods ......................... 15 R e s u l t s ...................................... 19 D i s c u s s i o n ................................... 24 S u m m a r y ...................................... 28 Refeirences ................................... 40 VI TABLE OF OOMTEMTS (Continued) Page CHAPTER III. VIRAL PEE^ISTEMCE IN VERO CRT.Tfi DUALLY INFECTED WITH IWD PARAMYXOVIRUSES: A MORPHOLOGICAL AND IMMUNOELECTRON MICROSCOPIC INVESTIGATION......... 45 Introduction................................. 45 Materials and Ifethods......................... 48 R e s u l t s ...................................... 52 D i s c u s s i o n .................................. 56 S u m m a r y ...................................... 59 R e f e r e n c e s .................................. 87 IV. PERSISTENT INFECTICN OF VERO rRT.Tfi BY PARAMYXOVIRUSES ................................ 91 Introduction................................. 91 Materials and tfethods......................... 93 R e s u l t s ...................................... 96 D i s c u s s i o n .................................. 99 S u m m a r y ...................................... 103 R e f e r e n