Acute experimental infection of bats and ferrets with Hendra virus: Insights into the early host response of the reservoir host and susceptible model species.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
03 2020
Historique:
received: 28 10 2019
accepted: 19 02 2020
revised: 09 04 2020
pubmed: 1 4 2020
medline: 23 6 2020
entrez: 1 4 2020
Statut: epublish

Résumé

Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come predominantly from in vitro studies focusing on innate immunity. Information on the early host response to infection in vivo is lacking and there is no comparative data on responses in bats compared with animals that succumb to disease. In this study, we examined the sites of HeV replication and the immune response of infected Australian black flying foxes and ferrets at 12, 36 and 60 hours post exposure (hpe). Viral antigen was detected at 60 hpe in bats and was confined to the lungs whereas in ferrets there was evidence of widespread viral RNA and antigen by 60 hpe. The mRNA expression of IFNs revealed antagonism of type I and III IFNs and a significant increase in the chemokine, CXCL10, in bat lung and spleen following infection. In ferrets, there was an increase in the transcription of IFN in the spleen following infection. Liquid chromatography tandem mass spectrometry (LC-MS/MS) on lung tissue from bats and ferrets was performed at 0 and 60 hpe to obtain a global overview of viral and host protein expression. Gene Ontology (GO) enrichment analysis of immune pathways revealed that six pathways, including a number involved in cell mediated immunity were more likely to be upregulated in bat lung compared to ferrets. GO analysis also revealed enrichment of the type I IFN signaling pathway in bats and ferrets. This study contributes important comparative data on differences in the dissemination of HeV and the first to provide comparative data on the activation of immune pathways in bats and ferrets in vivo following infection.

Identifiants

pubmed: 32226041
doi: 10.1371/journal.ppat.1008412
pii: PPATHOGENS-D-19-01983
pmc: PMC7145190
doi:

Substances chimiques

Antigens, Viral 0
Chemokine CXCL10 0
Interferons 9008-11-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008412

Déclaration de conflit d'intérêts

Amanda P. Woon is employed by Immunocore Ltd. The authors have declared that no competing interests exist.

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Auteurs

Amanda P Woon (AP)

Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Immunocore Ltd, Abingdon, Oxford, United Kingdom.

Victoria Boyd (V)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Shawn Todd (S)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Ina Smith (I)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Reuben Klein (R)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Isaac B Woodhouse (IB)

Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Centre of Innate Immunity and Infectious Diseases, Hudson Institute of Medical Search, Clayton, Victoria, Australia.

Sarah Riddell (S)

CSIRO, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Gary Crameri (G)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

John Bingham (J)

CSIRO, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Lin-Fa Wang (LF)

Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore.

Anthony W Purcell (AW)

Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

Deborah Middleton (D)

CSIRO, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

Michelle L Baker (ML)

CSIRO Health and Biosecurity Business Unit, Australian Animal Health Laboratory, Geelong, Victoria, Australia.

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Classifications MeSH