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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
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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.
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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
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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.
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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.
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Annual reports of OIE Reference Laboratories and Collaborating Centres, 2007
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