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Hendra and Nipah virus diseases Dr Peter W Daniels Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia Tel.: (61-3)52.27.50.00, Fax: (61-3)52.27.55.55 [email protected] Summary of general activities related to the disease 1. Test(s) in use/or available for the specified disease at your laboratory For Hendra virus (HeV) laboratory testing AAHL offers virus isolation, conventional PCR and TaqMan real time PCR, immunofluorescent antigen detection, histopathology and immunohistochemistry, electron microscopy and immuno-EM, characterization of isolates by sequence analysis and serology by ELISA and VNT under PC4 biocontainment. For Nipah virus (NiV) AAHL offers a similar range of tests. In 2007 the following tests were performed: 2. Test For Specificity Total HeV ELISA Antibody Group 217 NiV ELISA Antibody Group 390 HeV VNT Antibody Type 453 NiV VNT Antibody Type 984 Cell culture Virus isolation Virus Specific 133 HeV Real-time PCR Nucleic Acid Virus Specific 117 HeV Conventional PCR Nucleic Acid Virus Specific 2 NiV Real-time PCR Nucleic Acid Virus Specific 22 NiV Conventional PCR Nucleic Acid Virus Specific 0 HeV Immunohistochemistry Antigen Group 27 NiV Immunohistochemistry Antigen Group 13 Production and distribution of diagnostic reagents For both HeV and NiV diseases AAHL produces reagents for ELISA and immunological techniques. During the year HeV ELISA reagents sufficient for 10,000 tests were produced for use in Australian laboratories. Reagents for immunohistochemistry, including a Nipah virus positive parafin block and rabbit anti-Nipah virus antibody, were supplied to Thailand. ELISA reagent sufficient for 1000 NiV and HeV tests were supplied to Indonesia. Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007 1 Hendra and Nipah virus diseases Activities specifically related to the mandate of OIE Reference Laboratories 3. International harmonisation and standardisation of methods for diagnostic testing or the production and testing of vaccines Work has continues on validation of ELISA protocols for the detection of bat antibodies against henipaviruses, and for the detection of antibodies to Henipaviruses in domestic animal sera.. The data has been presented to AAHL’s Diagnostic Test Management Committee (DTMC) and is to be prepared for presentation to the national body, the Sub Committee of Animal Health Laboratory Standards (SCAHLS) Diagnostic assays based on Luminex technology have also been developed and standardized. The technology was transferred to a laboratory in Malaysia, indicating the reproducability of the test methods. 4. Preparation and supply of international reference standards for diagnostic tests or vaccines AAHL can supply standard reference materials for Hendra and Nipah viruses, and does so when transferring diagnostic test capability. 5. Research and development of new procedures for diagnosis and control AAHL maintains an active research program on the henipaviruses and related paramyxoviruses, as well as on other zoonoses and potential zoonoses carried by bats. Major lines of inquiry include : 6. development of novel antiviral treatments for Henipavirus infections optimization of novel Henipavirus vaccines development of an improved diagnostic capability for Henipavirus infections Paramyxovirus genetic systems Collection, analysis and dissemination of epizootiological data relevant to international disease control Support was given to bat sero-surveillance work in Malaysia, Indonesia & Australia. 7. Provision of consultant expertise to OIE or to OIE Member Countries AAHL staff have not participated in such formal provision of expertise this year. 8. Provision of scientific and technical training to personnel from other OIE Member Countries A colleague from the Central Institute for Animal Disease Control in Lelystad, Netherlands undertook training to establish Nipah diagnostics for 1 week 5-9 February 2007. 9. Provision of diagnostic testing facilities to other OIE Member Countries AAHL provides a serological testing service in support of animal movements in the region, with testing being conducted according to the requirements of a number of countries internationally. 10. Organisation of international scientific meetings on behalf of OIE or other international bodies AAHL and the Australian Association of Veterinary Laboratory Diagnosticians (AAVLD) hosted the 13th International Symposium of the World Association of Veterinary Laboratory Diagnosticians (WAVLD) in Melbourne, Australia from 11th to 14th November, 2007. Three invited plenary papers dealing with emerging infectious diseases dealt with henipaviruses and the challenges of managing the risk of disease emergence from wildlife hosts. 2 Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007 Hendra and Nipah virus diseases 11. Participation in international scientific collaborative studies Diagnostic assays based on Luminex technology have been transferred to a laboratory in Malaysia. AAHL continues to provide laboratory support to studies of the natural history of henipaviruses in Southeastern Asian countries. The collaborative study with the Department of Microbiology and Immunology, Uniformed Services University, Bethesda continued to examine the ability of peptides derived from the henipavirus fusion protein to inhibit viral replication. As reported previously peptides prepared under the project inhibited viral replication in cell culture and blocked cell fusion in an in vitro assay. Studies of their ability to ameliorate disease in an animal model has have been extended in a model of henipavirus infection in civets, which is considered a better model than the cat model. Their efficacy in both the cat and civet models was equivocal, with problems of how to deliver effective doses being seen as the issue. 12. Publication and dissemination of information relevant to the work of OIE (including list of scientific publications, internet publishing activities, presentations at international conferences) Presentations at international conferences and meetings Bossart KN. 2007. A comprehensive approach to henipavirus surveillance based on ecology, immunology and molecular pathogenesis. Workshop on Converging Technologies for Biosecurity. Australian Academy of Technological Sciences and Engineering, Melbourne. The Workshop. Calisher C, Wang LF. 2007. Diagnosis and control of emerging viral infections. 25th International Congress of Chemotherapy (ICC) and the 17th European Congress of Clinical Microbiology and Infectious Diseases. Munich, Germany. The Congress. Daniels PW. 2007. Nipah and Hendra viruses and Pteropid bats: more outbreaks, new observations, future challenges. IMED 2007 International Meeting on Emerging Diseases and Surveillance. Vienna, Austria. The Meeting. Middleton DJ. 2007. Application of biotechnology to infections with wildlife hosts. WAVLD 2007 Preparing for the animal health challenges of the future: 13th International World Association of Veterinary Laboratory Diagnosticians Symposium: symposium proceedings. Crown Promenade, Melbourne. The Symposium. Mungall BA, Middleton DJ, Eisen D. 2007. Plasma-derived mannose-binding lectin has in vitro activity against Henipa viruses. 1st Congress of the Society of Innate Immunity. Antalya, Turkey. The Congress. Mungall BA, Middleton DJ, Halpin K, Daniels PW, Bingham J. 2007. Experimental models for Henipavirus infection: bats, cats and pseudo-rats. WAVLD 2007 Preparing for the animal health challenges of the future: 13th International World Association of Veterinary Laboratory Diagnosticians Symposium: symposium proceedings. Crown Promenade, Melbourne. The Symposium. Wang LF. 2007. Virus-host cell interaction. ASM 2007 Annual Scientific Meeting of the Australian Society for Microbiology. Adelaide Convention Centre, Adelaide. The Meeting. Wang LF. 2007. Zoonotic viruses of bat origin - discovery and diagnosis. WAVLD 2007 Preparing for the animal health challenges of the future: 13th International World Association of Veterinary Laboratory Diagnosticians Symposium: symposium proceedings. Crown Promenade Melbourne. The Symposium. Scientific publications in peer-reviewed journals Bishop KA, Stantchev TS, Hickey AC, Khetawat D, Bossart KN, Krasnoperov V, Gill P, Feng YR, Wang LF, Eaton BT, Wang LF, Broder CC. 2007. Identification of Hendra virus G glycoprotein residues that are critical for receptor binding. Journal of Virology. 81: 5893-5901. Bossart KN, Bingham J, Middleton DJ. 2007. Targeted strategies for Henipavirus therapeutics. Open Virology Journal. 1: 14-25. Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007 3 Hendra and Nipah virus diseases Bossart KN, McEachern JA, Hickey AC, Choudhry V, Dimitrov DS, Eaton BT, Wang LF. 2007. Neutralization assays for differential henipavirus serology using Bio-Plex protein array systems. Journal of Virological Methods. 142: 29-40. Bossart KN, Tachedjian M, McEachern JA, Crameri G, Zhu Z, Dimitrov DS, Broder CC, Wang LF. 2007. Functional studies of host-specific ephrin-B ligands as Henipavirus receptors. Virology. online: Chen JM, Yaiw KC, Yu M, Wang LF, Wang QH, Crameri GS, Wang ZL. 2007. Expression of truncated phosphoproteins of Nipah virus and Hendra virus in Escherichia coli for the differentiation of henipavirus infections. Biotechnology Letters. 29: 871-875. Chua KB, Wong EMH, Cropp BC, Hyatt AD. 2007. Role of electron microscopy in Nipah virus outbreak investigation and control. Medical Journal of Malaysia. 62: 139. Daniels PW, Halpin K, Hyatt A, Middleton D. 2007. Infection and disease in reservoir and spillover hosts: determinants of pathogen emergence. Current Topics in Microbiology and Immunology. 315: 113-31. Dimitrov DS, Wang LF. 2007. In utero transmission of Nipah virus: role played by pregnancy and vertical transmission in Henipavirus epidemiology. Journal of Infectious Diseases. 196: 807-809. Fogarty R, Halpin K, Hyatt AD, Daszak P, Mungall BA. 2007. Henipavirus susceptibility to environmental variables. Virus Research. Online: Hagmaier K, Stock N, Precious B, Childs K, Wang LF, Goodbourn S, Randall RE. 2007. Mapuera virus, a Rubulavirus that inhibits interferon signalling in a wide variety of mammalian cells without degrading STATs. Journal of General Virology. 88: 956-66. Halpin K, Hyatt AD, Plowright RK, Epstein JH, Daszak P, Field HE, Wang LF, Daniels PW. 2007. Emerging viruses: coming in on a wrinkled wing and a prayer. Clinical Infectious Diseases. 44: 711-7. Halpin K, Mungall BA. 2007. Recent progress in henipavirus research. Comparative Immunology, Microbiology and Infectious Diseases. 30: 287-307. Juozapaitis M, Serva A, Kucinskaite I, Zvirbliene A, Slibinskas R, Staniulis J, Sasnauskas K, Shiell BJ, Bowden TR, Michalski WP. 2007. Generation of Menangle virus nucleocapsid-like particles in yeast Saccharomyces cerevisiae. Journal of Biotechnology. 130: 441-447. Juozapaitis M, Serva A, Zvirbliene A, Slibinskas R, Staniulis J, Sasnauskas K, Shiell BJ, Wang LF, Michalski WP. 2007. Generation of henipavirus nucleocapsid proteins in yeast Saccharomyces cerevisiae. Virus Research. 124: 95-102. Magoffin DE, Halpin K, Rota PA, Wang LF. 2007. Effects of single amino acid substitutions at the E residue in the conserved GDNE motif of the Nipah virus polymerase L protein. Archives of Virology. 152: 827-832. Magoffin DE, Mackenzie JS, Wang LF. 2007. Genetic analysis of J-virus and Beilong virus using minireplicons. Virology. 364: 103-111. Middleton DJ, Morrissy CJ, van der Heide BM, Russell GM, Braun MA, Westbury HA, Halpin K, Daniels PW. 2007. Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus). Journal of Comparative Pathology. 136: 266-272. Mungall BA, Middleton DJ, Crameri GS, Halpin K, Bingham J, Eaton BT, Broder CC. 2007. Vertical transmission and fetal replication on Nipah virus in an experimentally infected cat. Journal of Infectious Diseases. 196: 812-816. Porotto M, Carta P, Deng Y, Kellogg GE, Whitt M., Lu M, Mungall BA, Moscona A. 2007. Molecular determinants of antiviral potency of paramyxovirus entry inhibitors. Journal of Virology. 81: 10567-10574. 4 Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007 Hendra and Nipah virus diseases Wang LF, Hansson E, Yu M, Chua KB, Mathe N, Crameri GS, Rima BK, Moreno-Lopez J, Eaton BT. 2007. Fulllength genome sequence and genetic relationship of two paramyxoviruses isolated from bats and pigs in the Americas. Archives of Virology. 152: 1259-1271. Xiao C, Liu Y, Jiang Y, Magoffin DE, Guo H, Xuan H, Wang G, Wang LF, Tu C. 2007. Monoclonal antibodies against the nucleocapsid proteins of Henipaviruses: production, epitope mapping and application in immunochemistry. Archives of Virology. Online: Yaiw KC, Bingham J, Crameri GS, Mungall B, Hyatt AD, Eaton BT, Shamala D, Wang LF, Wong KT. 2007. Experimental Tioman virus infection in pigs. Malaysian Journal of Pathology. 29: 202. Yaiw KC, Crameri GS, Wang LF, Chong HT, Chua KB, Tan CT, Goh KJ, Shamala D, Wong KT. 2007. Serological evidence of possible human infection with Tioman virus, a newly described paramyxovirus of bat origin. Journal of Infectious Diseases. 196: 884-886. Yaiw KC, Ong KC, Chua KB, Bingham. J., Wang LF, Shamala D, Wong KT. 2007. Tioman virus infection in experimentally infected mouse brain and its association with apoptosis. Journal of Virological Methods. 143: 140146. Other communications – Books and Book Chapters Bossart KN, Broder CC. 2007. Paramyxovirus entry. Pohlmann, S, Simmons, G. (eds). Viral entry into host cells Landes Bioscience, Austin, Texas, USA. Eaton BT, Mackenzie JS, Wang LF. 2007. Henipaviruses. Knipe, DM, Griffin, DE, Lamb, RA, Straus, SE, Howley, PM, Martin, MA, Roizman, B. (eds). Field's virology Lippincott, Williams & Wilkins, Philadelphia, USA. Pp. 1587-1600. Schopman NCT. 2007. SiRNA Mediated Suppression of Nipah Virus Replication. Wageningen University, Wageningen, Netherlands. _______________ Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007 5