Outcomes
The research team is the first group in the world to examine bat transcriptome sequences in great detail. The data has proven to be very important to understand basic bat biology and immunology. The transcriptome datasets will also play a key role in assigning functions of different genes when the bat genome sequences become available from overseas collaborators. For further information, contact Dr Linfa Wang, Linfa.Wang@csiro.au.
Visionary Goal
From knowledge of bats and bat cell response to virus infection, we will develop new approaches and methods for surveillance, virus isolation and management of outbreaks caused by bat-borne viruses.
Background Statement
In Australia and around the world bats have been identified as natural reservoirs for an increasing number of viruses that are pathogenic for man and animals. Recent additions to the list of bat-borne viruses include Hendra virus, Nipah virus, Menangle virus, Australian bat lyssaviruses, Ebola virus and SARS (severe acute respiratory syndrome) coronavirus (CoV). Virus infection of bats is almost always asymptomatic, virus replication is frequently limited and generation of solid antibody responses is inconsistent. Factors responsible for the generation and maintenance of bat-virus equilibria are unknown.
We propose to sequence the transcriptome of two bat genera (Pteropus and Rhinolophus, reservoirs of Henipaviruses and SARS CoV respectively) and use bioinformatic analyses to identify and compare bat proteins with proteins known or believed to be involved in the immune response of other mammalian species. In this way it will be possible to rapidly and simultaneously identify functions such as interleukins, interferon response proteins, T cell receptors and other proteins involved in the adaptive and innate immune responses of bats. Once identified a hypothesis-driven research program will ascertain the functional role of these factors in the bat immune response to virus infection. It is anticipated that knowledge of the bat-virus relationship at a molecular level will greatly facilitate new approaches to surveillance, virus isolation and outbreak management. Hypotheses relevant to these goals will be explored in collaboration with national and international collaborators in the field of molecular cell biology and immunology.
The project will generate information that is not obtainable in any other way, which will facilitate development of hypotheses that relate directly to the three other currently funded AB-CRC projects that focus on bats. These are:
(1) Assessment of the risk of introduction of Nipah virus into Australia via flying foxes (2.012RE).
(2) Investigations of SARS-like coronaviruses in bats (2.026RE).
(3) Selection and validation of diagnostic assays for the detection of Henipaviruses (1.028R).
The underlying fundamental issue in the first two projects is our lack of knowledge of factors involved in virus persistence in bats and bat populations.
Objectives & Aims of Project
1 Acquire transcriptome sequence data for an Australian Rhinolophus and an Australian Pteropus species.
2. Mine the sequence data using published data bases to seek differences between bats and non-volant mammalian species in proteins known or believed to be involved in either adaptive and innate immune responses.
3 Develop hypotheses based on knowledge of the bat transcriptome to explain aspects of the bat-virus interaction. In the absence of data acquired in (1) and (2) it is not possible to be specific about the hypotheses to be developed. However, we expect for example to test hypotheses that explain how bats restrict replication of some viruses prior to appearance of antiviral antibody.
4. While some hypotheses may be explored by the current collaborators, depending on the skills, reagents and infrastructure required, it is expected that exploration of most hypotheses will take place with national and international collaborators.
5. Use knowledge of the bat-virus relationship at a molecular level to develop new approaches to surveillance, virus isolation and outbreak management (Pending on further funding in the 3rd year).
Deliverables
1. Acquisition of complete genetic (transcriptome) sequence information for two Australian bat species (Nov 07)
2. Comparison of bat sequences with those of other mammalian species, particularly the proteins known to be involved in innate and adaptive immunity and in cellular response to virus infection (April 08).
3. Development of hypotheses based on specific differences between bat and non-bat species to explain the lack of clinical response of bats to virus infection and the asymptomatic persistence of viruses in bats (Oct 08).
4. National/international linkages developed to explore hypotheses (Dec 08).
5. Information derived from hypotheses used to develop new methods to detect viruses in bats, facilitate surveillance and develop risk management strategies in response to the emergence of bat-borne diseases (Dec 09, pending on extension of funding in the 3rd year). |