Alston Virus, a Novel Paramyxovirus Isolated from Bats Causes Upper Respiratory Tract Infection in Experimentally Challenged Ferrets

Johnson, Rebecca; Tachedjian, Mary; Rowe, Brenton; Clayton, Bronwyn A.; Layton, Rachel; Bergfeld, Jemma; Wang, Lin‐Fa; Smith, Ina; Marsh, Glenn A.

doi:10.3390/v10120675

Cited by 13 publications

(12 citation statements)

References 39 publications

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“…The emergence of pathogenic paramyxoviruses, such as Nipah virus (NiV) and Hendra virus (HeV) (1), from native host reservoirs into human populations has driven recent efforts to survey virus prevalence in animals. Such investigations, especially those performed in bat populations (2–7), have revealed unexpected genomic breadth, expanding the number of genera within the Paramyxoviridae family (8, 9) and highlighting the potential for novel paramyxoviruses to spill over and threaten human health and animal husbandry.…”

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confidence: 99%

A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

Stelfox

Bowden

2019

Proc. Natl. Acad. Sci. U.S.A.

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The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutininneuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.virus-host interaction | viral attachment | paramyxovirus | structure | glycoprotein

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confidence: 99%

A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

Stelfox

Bowden

2019

Proc. Natl. Acad. Sci. U.S.A.

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“…For next-generation sequencing of whole viral genomes, purified viral RNA was concentrated using a RNA Clean & Concentrator™-5 kit (Zymo Research, Irvine, CA, USA) and RNA concentration was determined using a Qubit RNA HS assay kit read on a DeNovix DS-11FX Spectrophotometer/Fluorometer (DeNovix, Wilmington, DE, USA). Total RNA was reverse-transcribed then isothermally amplified using a REPLI-g WTA Single Cell kit (Qiagen, Hilden, Germany) as previously described (68). Dual barcoded Illumina libraries were prepared with the Nextera XT DNA kit according to the manufacturer’s protocol (Illumina, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Filoviruses Can Efficiently Infect Human Neuron-Like Cells Without Genetic Adaptation

McAuley

Tachedjian

Marsh

2019

Preprint

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7 Recent large-scale Ebola outbreaks, combined with improved follow-up of survivors, has 8 permitted the observation of common long-term neurological sequelae in patients that have 9 survived Ebola virus infection. To date there have been few studies into neurological 10 infections by Ebola or related filoviruses, however, recent studies have isolated infectious 11 virus from patients' cerebrospinal fluid months after being discharged from the treatment 12 facility. 13 14 In order to determine whether different filoviruses were capable of infecting human 15 neurons, the human neuroblastoma cell lines, SH-SY5Y and M17, were chemically-16 differentiated into more neuron-like cells using established protocols. The neuron-like 17 profiles of the differentiated cells were confirmed by the determination of expression of a 18 range of neuron-specific markers. Zaire ebolavirus, Reston ebolavirus, and Marburg virus 19 were serially-passaged in both cell lines to determine permissiveness of the cells, as well as 20 permit the acquisition of adaptive mutations in the viral genomes. Whilst Marburg virus 21 grew to high titres in both cell lines, Zaire ebolavirus only grew in SH-SY5Y cells, and Reston 22 ebolavirus rapidly died out in both cell lines. Whole-genome sequencing of the passaged 23 viruses revealed two consensus-level non-coding mutations in the SH-SY5Y-passaged 24 Marburg virus. Viral growth kinetics were determined for pre-and post-passaging Zaire 25 ebolavirus and Marburg virus in both human neuronal cell lines, as well as the human 26 hepatocyte cell line, Huh7. Growth kinetics were similar for both the pre-and post-passaged 27 viruses, suggesting that adaptive mutations were not required for efficient growth in these 28 cells.29 30 This study is the first to demonstrate that filoviruses are capable of infecting human neuron-31 like cells in a species-specific manner. Marburg virus-infected cells remained alive up to Day 32 21 post-infection, suggesting that long-term neurological sequelae following filovirus 33 infection may be a result of direct neuronal infection, and that infection of neurons might 34 contribute to viral persistence in survivors. 3536 Author Summary 37 Filoviruses, including Ebola and Marburg viruses, have been traditionally considered 38 "haemorrhagic fever" viruses, with infections causing bleeding and frequently death. Recent 39 large-scale outbreaks in Africa have challenged these assumptions due to a significant 40 number of patients reporting neurological symptoms sometimes months after infection. In 41 many of these patients, virus was present at detectable levels in the fluid surrounding the 42 brain. There has been significant debate about the ability of Ebola and Marburg viruses to 43 infect and grow in human neurons (brain cells), and evidence has been lacking due to the 44 lack of feasibility in taking brain samples. Our study demonstrates that both Zaire ebolavirus 3 45 and Marburg virus are capable of infecting cells derived from human brains without needing 46 to change, and...

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“…The bat-originating Mapuera virus is genetically and antigenically related to the porcine orthorubulavirus La Piedad Michoacán virus, which causes blue-eye pig disease ( 7 – 9 ). Similarly, Alston orthorubulavirus, which was isolated from bats, is genetically and antigenically closely related to parainfluenza virus 5, which infects humans, monkeys, and dogs ( 10 ). The mumps orthorubulavirus species includes both human and bat mumps viruses, which are considered conspecific due to their high genetic, antigenic, and functional similarities ( 11 ).…”

Section: Observationmentioning

confidence: 99%

Eptesicus fuscus Orthorubulavirus, a Close Relative of Human Parainfluenza Virus 4, Discovered in a Bat in South Dakota

2021

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Alston Virus, a Novel Paramyxovirus Isolated from Bats Causes Upper Respiratory Tract Infection in Experimentally Challenged Ferrets

Cited by 13 publications

References 39 publications

A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

Filoviruses Can Efficiently Infect Human Neuron-Like Cells Without Genetic Adaptation

Eptesicus fuscus Orthorubulavirus, a Close Relative of Human Parainfluenza Virus 4, Discovered in a Bat in South Dakota

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