WAVLD Symposium Handbook_V4.indd - csiro

World Association of Veterinary Laboratory Diagnosticians – 13 th International Symposium, Melbourne, Australia, 11-14 November 2007
1100 - 1230 Concurrent Session 1.1 - New & Emerging Diseases/Wildlife Mon
EXPERIMENTAL MODELS FOR HENIPAVIRUS INFECTION: BATS, CATS AND PSEUDO-RATS.
12
Bruce A. Mungall, Deborah J. Middleton, Kim Halpin, Peter Daniels, and John Bingham.
Australian Animal Health Laboratory, CSIRO Livestock Industries, 5 Portarlington Rd, Geelong, Australia
Introduction:
November
Hendra virus (HeV) and Nipah virus (NiV), comprising the genus Henipavirus, family Paramyxoviridae, have
been responsible for numerous outbreaks of zoonotic disease in livestock and humans. Bats of the genus
Pteropus have been identified as the reservoir hosts for these viruses. However, how virus spills over from
the reservoir host has remained a mystery. Nipah virus has continued to re-emerge in Asia, specifically
Bangladesh, since 2001, with case fatality rates as high as 92%. As there are no currently available vaccines
or antivirals indicated for Henipavirus infection, possible therapeutic and prophylactic options in the treatment
and prevention of Nipah virus disease has been seen as a priority in this field of research. In addition to
novel emerging pathogens, Henipaviruses are also BSL4 agents that possess several biological features
that make them highly adaptable for use as bioterror agents. Clearly, there is a high level of public health
importance attributed to Henipaviruses, and by inference, a considerable risk associated with new
emergence events by other unknown or as yet, uncharacterised paramyxoviruses.
Material & methods:
Understanding the amplifying host, the routes of transmission, the type of susceptible human hosts, and the
epicentres for zoonotic and human transmissions is crucial in the control of zoonotic infections. There have
been multiple recent paramyxovirus emergence events, many of these involving bats. Some of these newly
emerged viruses are highly pathogenic (henipaviruses), some are moderately pathogenic (Menangle, PoRV,
PPMV) while many are of unknown pathogenicity (Tioman, Mapuera, SalV, TPMV). The development or
characterization of animal models to study these newly identified viral zoonoses is important for
understanding their pathogenic features and in the development of therapeutics or vaccines. In order to
address the different angles of Henipavirus research, we have developed a range of experimental animal
models including bats, pigs, cats, guinea pigs and ferrets, all amenable to BSL4 conditions. This
presentation describes these models.
Results:
While the human symptoms of NiV infection range from fever and headache to severe acute febrile
encephalitis [1], the porcine disease is primarily a febrile respiratory illness with or without neurological signs
[3]. In both humans and pigs, NIV pathogenesis appears to be related to a systemic vasculitis [3, 5] and
experimental infection of cats, hamsters and ferrets has revealed a similar underlying pathology [3, 4, 6]
(Middleton, unpublished data). While guinea pigs have also been experimentally infected with HeV [2]
(Halpin et al., Manuscript in preparation) and NiV (Halpin et al., Manuscript in preparation), the pathology
differed significantly in several respects from the human cases and from naturally and experimentally
infected horses. NiV and HeV do not cause disease in mice even after subcutaneous administration, and
there is no serological evidence for NiV in rodents in Malaysia. However, and not surprisingly, HeV and NiV
will kill mice if administered intracranially but the lack of natural infection precludes the establishment of
useful rodent models.
Discussions & conclusions:
While the cat represents the animal model in which the pathology most closely resembles the lethal disease
course in humans, and will provide an excellent model for some studies, the ferret provides an excellent
more economical model for preliminary therapeutic testing. The high level of similarity between the two
viruses enables therapeutic studies to be carried out for both pathogens in parallel in ferrets followed by cats.
References:
1. Goh et al., Clinical features of Nipah virus encephalitis among pig farmers in Malaysia. N Engl J
Med, 2000. 342(17): p. 1229-35.
2. Hooper et al., Lesions of experimental equine morbillivirus pneumonia in horses. Veterinary
Pathology, 1997. 34: p. p312-322.
3. Middleton etal., Experimental Nipah virus infection in pigs and cats. J Comp Pathol, 2002. 126(2-3):
p. 124-36.
4. Mungall et al., Feline model of acute nipah virus infection and protection with a soluble glycoproteinbased
subunit vaccine. J Virol, 2006. 80(24): p. 12293-302.
5. Wong et al., Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral
zoonosis. Am J Pathol, 2002. 161(6): p. 2153-67.
6. Wong et al., A golden hamster model for human acute Nipah virus infection. Am J Pathol, 2003.
163(5): p. 2127-37.
Mon 12 November
World Association of Veterinary Laboratory Diagnosticians – 13 th International Symposium, Melbourne, Australia, 11-14 November 2007
THE EMERGENCE OF CANINE INFLUENZA IN THE USA: THE RELATIONSHIP TO
EQUINE INFLUENZA AND DEVELOPMENTS SINCE DISCOVERY IN 2004.
P.C. Crawford 1 , T.L. Anderson 1 , W.L. Castleman 1 , M.T. Long 1 , R.O. Donis 2 , T.E. Chambers 3 ,
E.P.J. Gibbs 1* .
1 College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
2 Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
3 OIE International Reference Laboratory for Equine Influenza, Gluck Equine Research Center, University of Kentucky, Lexington, KY,
USA.
In 2004, an influenza virus was isolated from an outbreak of severe respiratory diseases in racing
greyhounds at a track in Florida. Several dogs died of pulmonary haemorrhage. An influenza virus was
isolated and the entire genome was sequenced. It was concluded that all eight genes had originated from
equine influenza virus (H3N8), consistent with cross-species transfer from horse to dog. The details of the
discovery of canine influenza and the characterization of the virus have been published (Crawford et al.
2005, Science 310, 482-485). This paper reviews the features of subsequent outbreaks of canine influenza
in Florida and other states within the USA, and reports on the susceptibility of horses to the canine isolate.
Since 2004, canine influenza has been confirmed in multiple outbreaks of respiratory disease at greyhound
tracks throughout the USA and the virus has spread into the pet dog population, particularly those dogs
housed in shelters. The disease has been confirmed by serology and virus isolation in pet dogs in 25 states
in the contiguous USA. Molecular characterizations of recent isolates indicate that the virus is continuing to
evolve. Horses experimentally inoculated with the canine virus were infected as evidenced by
seroconversion and virus replication in pulmonary tissues, but clinical disease was mild.
The paper will discuss the relevance of this discovery to the recent epidemic of equine influenza in Australia.