117,998 research outputs found
Hendra in the Hunter Valley
No full textIn June 2019 the first equine case of Hendra virus in the Hunter Valley, New South Wales, Australia was detected. An urgent human and animal health response took place, involving biosecurity measures, contact tracing, promotion of equine vaccinations and investigation of flying fox activity in the area. No human or additional animal cases occurred. Equine vaccination uptake increased by over 30-fold in the surrounding region in the three months following the case. Black flying fox and grey-headed flying fox species were detected in the Valley. The incident prompted review of Hendra virus resources at local and national levels. This event near the “horse capital of Australia”, is the southernmost known equine Hendra case. Management of the event was facilitated by interagency collaboration involving human and animal health experts. Ongoing One Health partnerships are essential for successful responses to future zoonotic events.Full Tex
Surface density of the Hendra G protein modulates Hendra F protein-promoted membrane fusion: Role for Hendra G protein trafficking and degradation
No full textAbstractHendra virus, like most paramyxoviruses, requires both a fusion (F) and attachment (G) protein for promotion of cell–cell fusion. Recent studies determined that Hendra F is proteolytically processed by the cellular protease cathepsin L after endocytosis. This unique cathepsin L processing results in a small percentage of Hendra F on the cell surface. To determine how the surface densities of the two Hendra glycoproteins affect fusion promotion, we performed experiments that varied the levels of glycoproteins expressed in transfected cells. Using two different fusion assays, we found a marked increase in fusion when expression of the Hendra G protein was increased, with a 1:1 molar ratio of Hendra F:G on the cell surface resulting in optimal membrane fusion. Our results also showed that Hendra G protein levels are modulated by both more rapid protein turnover and slower protein trafficking than is seen for Hendra F
The equine Hendra virus vaccine remains a highly effective preventative measure against infection in horses and humans: ‘The imperative to develop a human vaccine for the Hendra virus in Australia’
No full textIn their commentary article, ‘The imperative to develop a human vaccine for the Hendra virus in Australia’, Zahoor and Mudie (1) argue the case for a human Hendra virus (HeV) vaccine. The statements supporting their arguments are incorrect and have the potential to cause infection ecology & epidemiology confusion and ultimately undermine confidence in current evidence-based risk management strategies, thereby placing equine and human lives at risk
Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes, Australia
No full textA novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans
Promotion of Hendra virus replication by microRNA 146a
No full textHendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease
Inhibition of cathepsin L and vesicular trafficking prevent cleavage of Hendra virus F.
No full text<p>(A) Vero cells or bat cells were transfected with pCAGGS-Hendra virus F and 24 hours post transfection, cells were metabolically labeled with Tran <sup>35</sup>S in the absence or presence of the indicated inhibitor. E64-d and cathepsin L inhibitor I were added at 20μM. Cells were lysed, immunoprecipitated and anaylzed on 10% SDS-PAGE. Arrow indicates the position of a novel band. (B, C) Cells transiently transfected with Hendra virus F (B) or PIV5 F (C) were labeled with Tran <sup>35</sup>S for 45 minutes and then chased for 3 hours at either 20°C or 37°C. Following lysis and immunoprecipitation, proteins were run on 10% SDS-PAGE and visualized by autoradiography.</p
A single amino acid substitution in the V protein of Nipah virus alters its ability to block interferon signalling in cells from different species
No full textThe V protein of the paramyxovirus Nipah virus (NiV) has been shown to antagonize the interferon (IFN) response in human cells via sequestration of STAT1 and STAT2. This study describes a mutant of the NiV V protein, referred to as V(AAHL), that is unable to antagonize IFN signalling and demonstrates that a single amino acid substitution is responsible for its inactivity. The molecular basis for this was identified as a failure to interact with STAT1 and STAT2. It was also shown that NiV V, but not V(AAHL), was functional as an IFN antagonist in human, monkey, rabbit, dog, horse, pig and bat cells, which suggests that the ability of NiV to block IFN signalling is not a major constraint that prevents this virus from crossing species barriers.</p
Residues in the Hendra Virus Fusion Protein Transmembrane Domain Are Critical for Endocytic Recycling
No full textABSTRACT
Hendra virus is a highly pathogenic paramyxovirus classified as a biosafety level four agent. The fusion (F) protein of Hendra virus is critical for promoting viral entry and cell-to-cell fusion. To be fusogenically active, Hendra virus F must undergo endocytic recycling and cleavage by the endosomal/lysosomal protease cathepsin L, but the route of Hendra virus F following internalization and the recycling signals involved are poorly understood. We examined the intracellular distribution of Hendra virus F following endocytosis and showed that it is primarily present in Rab5- and Rab4-positive endosomal compartments, suggesting that cathepsin L cleavage occurs in early endosomes. Hendra virus F transmembrane domain (TMD) residues S490 and Y498 were found to be important for correct Hendra virus F recycling, with the hydroxyl group of S490 and the aromatic ring of Y498 important for this process. In addition, changes in association of isolated Hendra virus F TMDs correlated with alterations to Hendra virus F recycling, suggesting that appropriate TMD interactions play an important role in endocytic trafficking.</jats:p
Human Hendra virus encephalitis associated with equine outbreak, Australia, 2008
No full textA recent Hendra virus outbreak at a veterinary clinic in Brisbane, Queensland, Australia, involved 5 equine and 2 human infections. In contrast to previous outbreaks, infected horses had predominantly encephalitic, rather than respiratory, signs. After an incubation period of 9-16 days, influenza-like illnesses developed in the 2 persons before progressing to encephalitis; 1 died. Both patients were given ribavirin. Basal serum and cerebrospinal fluid levels were 10-13 mg/L after intravenous administration and 6 mg/L after oral administration (isolate 90% inhibitory concentration 64 mg/L). Both patients were exposed to infected horses, 1 during the late incubation period in a horse. The attack rate for veterinary clinic staff exposed to infected horses was 10%. An isolate from this outbreak showed genetic heterogeneity with isolates from a concurrent, but geographically remote, outbreak and from previous outbreaks. Emergence of Hendra virus is a serious medical, veterinary, and public health challenge
Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro
No full textBackground: Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 M compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC), cytotoxicity (CC) and the in vitro therapeutic index in live virus and pseudotype assay formats. Results: While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion: All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies
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