The Experts below are selected from a list of 471 Experts worldwide ranked by ideXlab platform
J. Barrett - One of the best experts on this subject based on the ideXlab platform.
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Australian Bat Lyssavirus analysis of national Bat surveillance data from 2010 to 2016
Viruses, 2021Co-Authors: Rachel M Iglesias, Hume Field, Lee F Skerratt, Keren Coxwitton, J. BarrettAbstract:Australian Bat Lyssavirus (ABLV) was first described in 1996 and has been regularly detected in Australian Bats since that time. While the virus does not cause population level impacts in Bats and has minimal impacts on domestic animals, it does pose a public health risk. For this reason, Bats are monitored for ABLV and a national dataset is collated and maintained by Wildlife Health Australia. The 2010–2016 dataset was analysed using logistic regression and time-series analysis to identify predictors of infection status in Bats and the factors associated with human exposure to Bats. In common with previous passive surveillance studies, we found that little red flying-foxes (Pteropus scapulatus) are more likely than other species to be infected with ABLV. In the four Australian mainland species of flying-fox, there are seasonal differences in infection risk that may be associated with reproductive cycles, with summer and autumn the seasons of greatest risk. The risk of human contact was also seasonal, with lower risk in winter. In line with other studies, we found that the circumstances in which the Bat is encountered, such as exhibiting abnormal behaviour or being grounded, are risk factors for ABLV infection and human contact and should continue be key components of public health messaging. We also found evidence of biased recording of some types of information, which made interpretation of some findings more challenging. Strengthening of “One Health” linkages between public health and animal health services at the operational level could help overcome these biases in future, and greater harmonisation nationally would increase the value of the dataset.
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an unprecedented cluster of Australian Bat Lyssavirus in pteropus conspicillatus indicates pre flight flying fox pups are at risk of mass infection
Zoonoses and Public Health, 2020Co-Authors: J. Barrett, Hume Field, Lee F Skerratt, Alison Hoger, Kalpana Agnihotri, Jane Oakey, J Meers, Craig S SmithAbstract:: In November 2017, two groups of P. conspicillatus pups from separate locations in Far North Queensland presented with neurological signs consistent with Australian Bat Lyssavirus (ABLV) infection. These pups (n = 11) died over an 11-day period and were submitted to a government laboratory for testing where ABLV infection was confirmed. Over the next several weeks, additional ABLV cases in flying foxes in Queensland were also detected. Brain tissue from ABLV-infected flying foxes during this period, as well as archived brain tissue, was selected for next-generation sequencing. Phylogenetic analysis suggests that the two groups of pups were each infected from single sources. They were likely exposed while in creche at night as their dams foraged. This study identifies creche-age pups at a potentially heightened risk for mass ABLV infection.
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Dispatches Australian Bat Lyssavirus Infection in a Captive Juvenile Black Flying Fox
2013Co-Authors: Hume Field, Brad Mccall, J. BarrettAbstract:The newly emerging Australian Bat Lyssavirus causes rabieslike disease in Bats and humans. A captive juvenile black flying fox exhibited progressive neurologic signs, including sudden aggression, vocalization, dysphagia, and paresis over 9 days and then died. At necropsy, Lyssavirus infection was diagnosed by fluorescent antibody test, immunoperoxidase staining, polymerase chain reaction, and virus isolation. Eight human contacts received postexposure vaccination. Australia was considered free of rabies and the rabieslike viruses of the genus Lyssavirus until the recognition in 1996 of Australian Bat Lyssavirus (ABL) as the cause of a rabieslike disease in a black flying fox (Pteropus alecto)(1) and a wildlife caretaker (2). While serotypic, antigenic, and sequence analysis show that ABL is closely related to classic rabies virus and European Bat Lyssavirus (1), phylogenetic analysis has clearly demonstrated that ABL represents a new genotype, genotype 7 (3). Australia is still considered free of terrestrial (genotype 1) classic rabies (4). Rabies vaccine and antirabies immunoglobulin protect laboratory animals against ABL infection (5), and their use pre- and post-ABL exposure is recommended for humans (6,7). On the morning of December 8, 1997, two juvenile black flying foxes were found clinging to each other and vocalizing in a residential area near an urban flying fox colony. An experienced, rabies-vaccinated wildlife caretaker retrieved the two animals from an unusually low tree roost. On the basis of body weight and forearm measurements, their age was estimated at 2 to 3 weeks, an age of total maternal dependency. Their physical condition was normal. Both animals, Bat 1 (male) and Bat 2 (female), remained with the original caretake
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Australian Bat Lyssavirus: Observations of Natural and Experimental Infection in Bats
2005Co-Authors: J. Barrett, R. Lunt, Greg Smith, R. Barry, C. Rupprecht, Peter L. YoungAbstract:This conference abstract gives data and conclusions arising from targeted surveillance of wild Bats for naturally occuring Australian Bat Lyssavirus (ABLV) infection and other central nervous system diseases. It also provides data and conclusions arising from experimental infection of 10 Greyheaded flying foxes (Pteropus poliocephalus).
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Potential exposure to Australian Bat Lyssavirus, Queensland, 1996-1999.
Emerging infectious diseases, 2000Co-Authors: Brad J Mccall, J. Barrett, Jonathan H. Epstein, A. S. Neill, K. Heel, Greg A. Smith, Linda A. Selvey, B. Rodwell, R. LuntAbstract:Two human deaths caused by Australian Bat Lyssavirus (ABL) infection have been reported since 1996. Information was obtained from 205 persons (mostly adults from south Brisbane and the South Coast of Queensland), who reported potential ABL exposure to the Brisbane Southside Public Health Unit from November 1,1996, to January 31, 1999. Volunteer animal handlers accounted for 39% of potential exposures, their family members for 12%, professional animal handlers for 14%, community members who intentionally handled Bats for 31%, and community members with contacts initiated by Bats for 4%. The prevalence of Lyssavirus detected by fluorescent antibody test in 366 sick, injured, or orphaned Bats from the area was 6%. Sequelae of exposure, including the requirement for expensive postexposure prophylaxis, may be reduced by educating Bat handlers and the public of the risks involved in handling Australian Bats.
Hume Field - One of the best experts on this subject based on the ideXlab platform.
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Australian Bat Lyssavirus analysis of national Bat surveillance data from 2010 to 2016
Viruses, 2021Co-Authors: Rachel M Iglesias, Hume Field, Lee F Skerratt, Keren Coxwitton, J. BarrettAbstract:Australian Bat Lyssavirus (ABLV) was first described in 1996 and has been regularly detected in Australian Bats since that time. While the virus does not cause population level impacts in Bats and has minimal impacts on domestic animals, it does pose a public health risk. For this reason, Bats are monitored for ABLV and a national dataset is collated and maintained by Wildlife Health Australia. The 2010–2016 dataset was analysed using logistic regression and time-series analysis to identify predictors of infection status in Bats and the factors associated with human exposure to Bats. In common with previous passive surveillance studies, we found that little red flying-foxes (Pteropus scapulatus) are more likely than other species to be infected with ABLV. In the four Australian mainland species of flying-fox, there are seasonal differences in infection risk that may be associated with reproductive cycles, with summer and autumn the seasons of greatest risk. The risk of human contact was also seasonal, with lower risk in winter. In line with other studies, we found that the circumstances in which the Bat is encountered, such as exhibiting abnormal behaviour or being grounded, are risk factors for ABLV infection and human contact and should continue be key components of public health messaging. We also found evidence of biased recording of some types of information, which made interpretation of some findings more challenging. Strengthening of “One Health” linkages between public health and animal health services at the operational level could help overcome these biases in future, and greater harmonisation nationally would increase the value of the dataset.
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an unprecedented cluster of Australian Bat Lyssavirus in pteropus conspicillatus indicates pre flight flying fox pups are at risk of mass infection
Zoonoses and Public Health, 2020Co-Authors: J. Barrett, Hume Field, Lee F Skerratt, Alison Hoger, Kalpana Agnihotri, Jane Oakey, J Meers, Craig S SmithAbstract:: In November 2017, two groups of P. conspicillatus pups from separate locations in Far North Queensland presented with neurological signs consistent with Australian Bat Lyssavirus (ABLV) infection. These pups (n = 11) died over an 11-day period and were submitted to a government laboratory for testing where ABLV infection was confirmed. Over the next several weeks, additional ABLV cases in flying foxes in Queensland were also detected. Brain tissue from ABLV-infected flying foxes during this period, as well as archived brain tissue, was selected for next-generation sequencing. Phylogenetic analysis suggests that the two groups of pups were each infected from single sources. They were likely exposed while in creche at night as their dams foraged. This study identifies creche-age pups at a potentially heightened risk for mass ABLV infection.
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evidence of Australian Bat Lyssavirus infection in diverse Australian Bat taxa
Zoonoses and Public Health, 2018Co-Authors: Hume FieldAbstract:Historically, Australia was considered free of rabies and rabieslike viruses. Thus, the identification of Australian Bat Lyssavirus (ABLV) in 1996 in a debilitated Bat found by a member of the public precipitated both public health consternation and a revision of Lyssavirus taxonomy. Subsequent observational studies sought to elaborate the occurrence and frequency of ABLV infection in Australian Bats. This paper describes the taxonomic diversity of Bat species showing evidence of ABLV infection to better inform public health considerations. Blood and/or brain samples were collected from two cohorts of Bats (wild-caught and diagnostic submissions) from four Australian states or territories between April 1996 and October 2002. Fresh brain impression smears were tested for ABLV antigen using fluorescein-labelled anti-rabies monoclonal globulin (CENTOCOR) in a direct fluorescent antibody test; sera were tested for the presence of neutralising antibodies using a rapid fluorescent focus inhibition test. A total of 3,217 samples from 2,633 Bats were collected and screened: brain samples from 1,461 wild-caught Bats and 1,086 submitted Bats from at least 16 genera and seven families, and blood samples from 656 wild-caught Bats and 14 submitted Bats from 14 genera and seven families. Evidence of ABLV infection was found in five of the six families of Bats occurring in Australia, and in three of the four Australian states/territories surveyed, supporting the historic presence of the virus in Australia. While the infection prevalence in the wild-caught cohort is evidently low, the significantly higher infection prevalence in rescued Bats in urban settings represents a clear and present public health significance because of the higher risk of human exposure.
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Australian Bat Lyssavirus
Australian journal of general practice, 2018Co-Authors: Tony Merritt, Hume Field, Kathryn Taylor, Keren Cox-witton, Kate Wingett, Diana Mendez, Michelle L. Power, David N. DurrheimAbstract:Australian Bat Lyssavirus (ABLV) causes human illness that is indistinguishable from classical rabies. All Australian Bats have the potential to carry and transmit ABLV, and potentially risky human exposures to Bats are common. ABLV infection has resulted in three human deaths in Australia since 1996. The aim of this article is to equip general practitioners (GPs) to assist in the prevention and management of potential ABLV exposures in Australia, including complex clinical scenarios that are not fully addressed in current national guidelines. Potential ABLV exposures are frequently encountered in general practice. GPs play a critical role in risk mitigation for groups such as veterinarians and wildlife carers, and in triggering urgent multidisciplinary responses to potential exposures. Timely notification of the public health unit following a potential exposure is crucial to ensure appropriate assessment and access to correct treatment. Complex exposure scenarios require careful consideration.
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Dispatches Australian Bat Lyssavirus Infection in a Captive Juvenile Black Flying Fox
2013Co-Authors: Hume Field, Brad Mccall, J. BarrettAbstract:The newly emerging Australian Bat Lyssavirus causes rabieslike disease in Bats and humans. A captive juvenile black flying fox exhibited progressive neurologic signs, including sudden aggression, vocalization, dysphagia, and paresis over 9 days and then died. At necropsy, Lyssavirus infection was diagnosed by fluorescent antibody test, immunoperoxidase staining, polymerase chain reaction, and virus isolation. Eight human contacts received postexposure vaccination. Australia was considered free of rabies and the rabieslike viruses of the genus Lyssavirus until the recognition in 1996 of Australian Bat Lyssavirus (ABL) as the cause of a rabieslike disease in a black flying fox (Pteropus alecto)(1) and a wildlife caretaker (2). While serotypic, antigenic, and sequence analysis show that ABL is closely related to classic rabies virus and European Bat Lyssavirus (1), phylogenetic analysis has clearly demonstrated that ABL represents a new genotype, genotype 7 (3). Australia is still considered free of terrestrial (genotype 1) classic rabies (4). Rabies vaccine and antirabies immunoglobulin protect laboratory animals against ABL infection (5), and their use pre- and post-ABL exposure is recommended for humans (6,7). On the morning of December 8, 1997, two juvenile black flying foxes were found clinging to each other and vocalizing in a residential area near an urban flying fox colony. An experienced, rabies-vaccinated wildlife caretaker retrieved the two animals from an unusually low tree roost. On the basis of body weight and forearm measurements, their age was estimated at 2 to 3 weeks, an age of total maternal dependency. Their physical condition was normal. Both animals, Bat 1 (male) and Bat 2 (female), remained with the original caretake
Christopher C Broder - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of cross reactive human monoclonal antibodies that potently neutralize Australian Bat Lyssavirus variants and other phylogroup 1 Lyssaviruses
2021Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Christopher C Broder, Wanda Markotter, Jessica Coertse, Siana Coggins, Lianying Yan, Brian C SchaeferAbstract:Australian Bat Lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid Bats (ABLVp) and the yellow-bellied sheath-tailed Bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, administration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.39 and 6.25 µg/mL and 0.19 and 0.39 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the Lyssavirus G protein, effectively neutralizing phylogroup 1 Lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse Lyssaviruses. These results suggest that A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 Lyssavirus infections.
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enhanced autophagy contributes to reduced viral infection in black flying fox cells
Viruses, 2019Co-Authors: Eric D Laing, Spencer L Sterling, Dawn L Weir, Chelsi R Beauregard, Sasha E Larsen, Ina Smith, Brian C Schaefer, Andrew L. Snow, Linfa Wang, Christopher C BroderAbstract:Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian Bat Lyssavirus (ABLV) infection, viral replication is dampened in these Bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in Bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling Bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for comBating Lyssavirus infection.
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host cell virus entry mediated by Australian Bat Lyssavirus g envelope glycoprotein occurs through a clathrin mediated endocytic pathway that requires actin and rab5
Virology Journal, 2014Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Linfa Wang, Christopher C BroderAbstract:Background Australian Bat Lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit Bats and insectivorous Bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined.
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host cell virus entry mediated by Australian Bat Lyssavirus g envelope glycoprotein occurs through a clathrin mediated endocytic pathway that requires actin and rab5
Virology Journal, 2014Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Linfa Wang, Christopher C BroderAbstract:Australian Bat Lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit Bats and insectivorous Bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined. ABLV internalization into HEK293T cells was examined using maxGFP-encoding recombinant vesicular stomatitis viruses (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular approaches was used to investigate the contribution of different endocytic pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the endosomal compartment utilized by ABLV to gain entry into the host cell cytosol. Here we show that ABLV G-mediated entry into HEK293T cells was significantly inhibited by the dynamin-specific inhibitor dynasore, chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin depolymerizing drug latrunculin B. Over expression of dominant negative mutants of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry. The predominant pathway utilized by ABLV for internalization into HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for productive infection indicates that ABLV G-mediated fusion occurs within the early endosome compartment.
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recent observations on Australian Bat Lyssavirus tropism and viral entry
Viruses, 2014Co-Authors: Dawn L Weir, Edward J Annand, Peter A Reid, Christopher C BroderAbstract:Australian Bat Lyssavirus (ABLV) is a recently emerged rhabdovirus of the genus Lyssavirus considered endemic in Australian Bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous Bats (genus Pteropus) and the other in insectivorous microBats (genus Saccolaimus). Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incuBation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than Bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G). Recent studies have revealed that proposed rabies virus (RABV) receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.
Ina Smith - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of cross reactive human monoclonal antibodies that potently neutralize Australian Bat Lyssavirus variants and other phylogroup 1 Lyssaviruses
2021Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Christopher C Broder, Wanda Markotter, Jessica Coertse, Siana Coggins, Lianying Yan, Brian C SchaeferAbstract:Australian Bat Lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid Bats (ABLVp) and the yellow-bellied sheath-tailed Bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, administration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.39 and 6.25 µg/mL and 0.19 and 0.39 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the Lyssavirus G protein, effectively neutralizing phylogroup 1 Lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse Lyssaviruses. These results suggest that A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 Lyssavirus infections.
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enhanced autophagy contributes to reduced viral infection in black flying fox cells
Viruses, 2019Co-Authors: Eric D Laing, Spencer L Sterling, Dawn L Weir, Chelsi R Beauregard, Sasha E Larsen, Ina Smith, Brian C Schaefer, Andrew L. Snow, Linfa Wang, Christopher C BroderAbstract:Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian Bat Lyssavirus (ABLV) infection, viral replication is dampened in these Bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in Bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling Bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for comBating Lyssavirus infection.
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assessment of a rabies virus rapid diagnostic test for the detection of Australian Bat Lyssavirus
Tropical Medicine and Infectious Disease, 2018Co-Authors: Andrea Certoma, Ina Smith, Ross A. Lunt, Wilna Vosloo, Axel Colling, David T Williams, Thao Tran, Stuart D. BlacksellAbstract:Australian Bat Lyssavirus (ABLV) is closely related to the classical rabies virus and has been associated with three human fatalities and two equine fatalities in Australia. ABLV infection in humans causes encephalomyelitis, resulting in fatal disease, but has no effective therapy. The virus is maintained in enzootic circulation within fruit Bats (Pteropid spp.) and at least one insectivorous Bat variety (Saccolaimus flaviventris). Most frequently, laboratory testing is conducted on pteropodid Bat brains, either following a potential human exposure through bites, scratches and other direct contacts with Bats, or as opportunistic assessment of sick or dead Bats. The level of medical intervention and post-exposure prophylaxis is largely determined on laboratory testing for antigen/virus as the demonstrable infection status of the in-contact Bat. This study evaluates the comparative diagnostic performance of a lateral flow test, Anigen Rabies Ag detection rapid test (RDT), in pteropodid variant of ABLV-infected Bat brain tissues. The RDT demonstrated 100% agreement with the reference standard fluorescent antibody test on 43 clinical samples suggesting a potential application in rapid diagnosis of pteropodid variant of ABLV infection. A weighted Kappa value of 0.95 confirmed a high level of agreement between both tests.
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Australian Bat Lyssavirus
2016Co-Authors: Greg Smith, Ina Smith, Peter R. MooreAbstract:There are two distinct strains of ABLV. One is found in the insectivorous Bat (Yb-ABLV) Saccolaimus aviventris, commonly known as the yellow-bellied sheathtail Bat belonging to the suborder Microchiroptera. The second, in ying foxes (Pt-ABLV) belonging to the Pteropus genus of the suborder Megachiroptera [11,12]. Australian Bat Lyssavirus isolates have been recovered from all four ying fox species native to mainland Australia: the black ying fox Pteropus alecto, the spectacled ying fox Pteropus conspicillatus, the grey headed ying fox Pteropus poliocephalus, and the little red ying fox Pteropus scapulatus. Among the pteropid strains of ABLV there is a low-genetic variance between isolates from different ying fox species as seen by identical G-gene sequences from ABLV isolates obtained from two different ying-fox species recovered 700 km apart [11]. This is believed to be due to mixed colonies and the large ight range of these ying foxes. This is consistent with our own observations comparing whole genomic sequences of different ABLV isolates (unpublished).
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host cell virus entry mediated by Australian Bat Lyssavirus g envelope glycoprotein occurs through a clathrin mediated endocytic pathway that requires actin and rab5
Virology Journal, 2014Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Linfa Wang, Christopher C BroderAbstract:Background Australian Bat Lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit Bats and insectivorous Bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined.
Linfa Wang - One of the best experts on this subject based on the ideXlab platform.
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phenotypic divergence of p proteins of Australian Bat Lyssavirus lineages circulating in microBats and flying foxes
Viruses, 2021Co-Authors: Celine Deffrasnes, Linfa Wang, Mengxiao Luo, Linda Wiltzerbach, Cassandra T David, Kim G Lieu, David A Jans, Glenn A Marsh, Gregory W MoseleyAbstract:Bats are reservoirs of many pathogenic viruses, including the Lyssaviruses rabies virus (RABV) and Australian Bat Lyssavirus (ABLV). Lyssavirus strains are closely associated with particular host reservoir species, with evidence of specific adaptation. Associated phenotypic changes remain poorly understood but are likely to involve phosphoprotein (P protein), a key mediator of the intracellular virus-host interface. Here, we examine the phenotype of P protein of ABLV, which circulates as two defined lineages associated with frugivorous and insectivorous Bats, providing the opportunity to compare proteins of viruses adapted to divergent Bat species. We report that key functions of P protein in the antagonism of interferon/signal transducers and activators of transcription 1 (STAT1) signaling and the capacity of P protein to undergo nuclear trafficking differ between lineages. Molecular mapping indicates that these differences are functionally distinct and appear to involve modulatory effects on regulatory regions or structural impact rather than changes to defined interaction sequences. This results in partial but significant phenotypic divergence, consistent with "fine-tuning" to host biology, and with potentially distinct properties in the virus-host interface between Bat families that represent key zoonotic reservoirs.
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enhanced autophagy contributes to reduced viral infection in black flying fox cells
Viruses, 2019Co-Authors: Eric D Laing, Spencer L Sterling, Dawn L Weir, Chelsi R Beauregard, Sasha E Larsen, Ina Smith, Brian C Schaefer, Andrew L. Snow, Linfa Wang, Christopher C BroderAbstract:Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian Bat Lyssavirus (ABLV) infection, viral replication is dampened in these Bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in Bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling Bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for comBating Lyssavirus infection.
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host cell virus entry mediated by Australian Bat Lyssavirus g envelope glycoprotein occurs through a clathrin mediated endocytic pathway that requires actin and rab5
Virology Journal, 2014Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Linfa Wang, Christopher C BroderAbstract:Background Australian Bat Lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit Bats and insectivorous Bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined.
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host cell virus entry mediated by Australian Bat Lyssavirus g envelope glycoprotein occurs through a clathrin mediated endocytic pathway that requires actin and rab5
Virology Journal, 2014Co-Authors: Dawn L Weir, Eric D Laing, Ina Smith, Linfa Wang, Christopher C BroderAbstract:Australian Bat Lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit Bats and insectivorous Bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined. ABLV internalization into HEK293T cells was examined using maxGFP-encoding recombinant vesicular stomatitis viruses (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular approaches was used to investigate the contribution of different endocytic pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the endosomal compartment utilized by ABLV to gain entry into the host cell cytosol. Here we show that ABLV G-mediated entry into HEK293T cells was significantly inhibited by the dynamin-specific inhibitor dynasore, chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin depolymerizing drug latrunculin B. Over expression of dominant negative mutants of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry. The predominant pathway utilized by ABLV for internalization into HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for productive infection indicates that ABLV G-mediated fusion occurs within the early endosome compartment.
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host cell tropism mediated by Australian Bat Lyssavirus envelope glycoproteins
Virology, 2013Co-Authors: Dawn L Weir, Ina Smith, Linfa Wang, Katharine N Bossart, Christopher C BroderAbstract:Australian Bat Lyssavirus (ABLV) is a rhabdovirus of the Lyssavirus genus capable of causing fatal rabies-like encephalitis in humans. There are two variants of ABLV, one circulating in pteropid fruit Bats and another in insectivorous Bats. Three fatal human cases of ABLV infection have been reported with the third case in 2013. Importantly, two equine cases also arose in 2013; the first occurrence of ABLV in a species other than Bats or humans. We examined the host cell entry of ABLV, characterizing its tropism and exploring its cross-species transmission potential using maxGFP-encoding recombinant vesicular stomatitis viruses that express ABLV G glycoproteins. Results indicate that the ABLV receptor(s) is conserved but not ubiquitous among mammalian cell lines and that the two ABLV variants can utilize alternate receptors for entry. Proposed rabies virus receptors were not sufficient to permit ABLV entry into resistant cells, suggesting that ABLV utilizes an unknown alternative receptor(s).
