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      Cedar Virus: A Novel Henipavirus Isolated from Australian Bats

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          Abstract

          The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir. Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses. The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin- B2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein. Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV.

          Author Summary

          Hendra and Nipah viruses are 2 highly pathogenic paramyxoviruses that have emerged from bats within the last two decades. Both are capable of causing fatal disease in both humans and many mammal species. Serological and molecular evidence for henipa-like viruses have been reported from numerous locations including Asia and Africa, however, until now no successful isolation of these viruses have been reported. This paper reports the isolation of a novel paramyxovirus, named Cedar virus, from fruit bats in Australia. Full genome sequencing of this virus suggests a close relationship with the henipaviruses. Antibodies to Cedar virus were shown to cross react with, but not cross neutralize Hendra or Nipah virus. Despite this close relationship, when Cedar virus was tested in experimental challenge models in ferrets and guinea pigs, we identified virus replication and generation of neutralizing antibodies, but no clinical disease was observed. As such, this virus provides a useful reference for future reverse genetics experiments to determine the molecular basis of the pathogenicity of the henipaviruses.

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          Most cited references36

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          A morbillivirus that caused fatal disease in horses and humans.

          A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
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            Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission.

            Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated.
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              Isolation of Nipah virus from Malaysian Island flying-foxes.

              In late 1998, Nipah virus emerged in peninsular Malaysia and caused fatal disease in domestic pigs and humans and substantial economic loss to the local pig industry. Surveillance of wildlife species during the outbreak showed neutralizing antibodies to Nipah virus mainly in Island flying-foxes (Pteropus hypomelanus) and Malayan flying-foxes (Pteropus vampyrus) but no virus reactive with anti-Nipah virus antibodies was isolated. We adopted a novel approach of collecting urine from these Island flying-foxes and swabs of their partially eaten fruits. Three viral isolates (two from urine and one from a partially eaten fruit swab) that caused Nipah virus-like syncytial cytopathic effect in Vero cells and stained strongly with Nipah- and Hendra-specific antibodies were isolated. Molecular sequencing and analysis of the 11,200-nucleotide fragment representing the beginning of the nucleocapsid gene to the end of the glycoprotein gene of one isolate confirmed the isolate to be Nipah virus with a sequence deviation of five to six nucleotides from Nipah virus isolated from humans. The isolation of Nipah virus from the Island flying-fox corroborates the serological evidence that it is one of the natural hosts of the virus.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                1553-7366
                1553-7374
                August 2012
                August 2012
                2 August 2012
                06 August 2012
                : 8
                : 8
                : e1002836
                Affiliations
                [1 ]CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Australia
                [2 ]Queensland Centre for Emerging Infectious Diseases, Biosecurity Queensland, Coopers Plain, Australia
                Mount Sinai School of Medicine, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GAM MT DM VH GC HEF LFW. Performed the experiments: GAM CdJ JAB MT CS DM MY ST AJF VH JP RR IB GC. Analyzed the data: GAM JAB MT DM GC LFW. Contributed reagents/materials/analysis tools: GAM CdJ JAB CS MY. Wrote the paper: GAM MT DM GC LFW.

                Article
                PPATHOGENS-D-12-00286
                10.1371/journal.ppat.1002836
                3410871
                22879820
                a2df680e-d4c0-4617-bb22-a5bce840788c
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 December 2011
                : 19 June 2012
                Page count
                Pages: 11
                Funding
                This study is supported in part by an OCE Postdoctoral Fellowship (GAM) and a CEO Science Leader Award (LFW) from the CSIRO Office of the Chief Executive, and a research grant from the Australian Government Wildlife and Exotic Diseases Preparedness Program (HEF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Microbiology
                Virology
                Emerging Viral Diseases
                Emerging Infectious Diseases
                Veterinary Science
                Veterinary Diseases
                Veterinary Virology

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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