Host cell tropism mediated by Australian bat lyssavirus envelope glycoproteins

Weir, Dawn L.; Smith, Ina; Bossart, Katharine N.; Wang, Lin‐Fa; Broder, Christopher C.

doi:10.1016/j.virol.2013.06.016

Cited by 11 publications

(24 citation statements)

References 39 publications

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“…One such cell line, CHOK1 cells, were previously reported to be highly permissive to the CVS-11 strain of RABV [29], suggesting that ABLV and RABV may utilize alternate receptors for host cell entry. We confirmed the high susceptibility of CHOK1 cells to RABV CVS-11 G-mediated viral entry and also found that PCI-13 cells, another ABLV resistant line, were also highly permissive to RABV G-mediated entry [30]. Both CHOK1 and PCI-13 cells were shown to express the proposed RABV protein receptors nAchR and NCAM, indicating that nAchR and NCAM are not sufficient to allow host cell entry of ABLV.…”

Section: Lyssavirus Entrysupporting

confidence: 66%

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Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

Weir

Annand

Reid³

et al. 2014

Viruses

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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.

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Section: Lyssavirus Entrysupporting

confidence: 66%

“…Interestingly, we found that the same is true for Saccolaimus and Pteropus variants of ABLV which showed a 6 to 45-fold difference in infectivity in three different cell lines derived from three different species [30]. These recent findings highlight the need for further research on lyssavirus entry.…”

Section: Lyssavirus Entrymentioning

confidence: 64%

Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

Weir

Annand

Reid³

et al. 2014

Viruses

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“…Contact between domestic dogs and ABLV infected bats has been reported previously [27], and our data indicate occasional pet animal-bat interactions (dogs/cats attacking bats on 62 occasions). Molecular studies on lyssavirus host cell entry mechanisms have found that ABLV host cell receptor is broadly conserved among mammals [28], indicating these animals are likely to be susceptible to ABLV infection. Future research is needed to better understand the potential transmission of ABLV from bats to domestic animals and implications for public health.…”

Section: Discussionmentioning

confidence: 99%

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014

Marquess

Donnan

et al. 2016

PLoS Negl Trop Dis

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BackgroundAustralian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV.Methodology/Principal FindingsPotential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat).Conclusions/SignificancePublic health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur.

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“…Recombinant maxGFP expressing vesicular stomatitis viruses (rVSV) that express ABLV G, Ebola Zaire GP, and VSV (Indiana) G glycoproteins have been previously described [6]. VSVΔG-G*-RFP pseudovirus stocks were kindly provided by Michael Whitt (University of Tennessee).…”

Section: Methodsmentioning

confidence: 99%

Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5

Weir

Laing

Smith

et al. 2014

Virol J

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BackgroundAustralian 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.MethodsABLV 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.ResultsHere 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.ConclusionsThe 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

Cited by 11 publications

References 39 publications

Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014

Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5

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