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      Reservoir Host Immune Responses to Emerging Zoonotic Viruses

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          Abstract

          Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance.

          Abstract

          Zoonotic viruses are emerging from the wild and causing serious disease in humans. Understanding how host reservoirs are able to tolerate the infection and spread the virus is a key element to informing new approaches for treating and preventing zoonotic diseases.

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          Most cited references78

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          Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

          A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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            The virome in mammalian physiology and disease.

            The virome contains the most abundant and fastest mutating genetic elements on Earth. The mammalian virome is constituted of viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect the broad array of other types of organisms that inhabit us. Virome interactions with the host cannot be encompassed by a monotheistic view of viruses as pathogens. Instead, the genetic and transcriptional identity of mammals is defined in part by our coevolved virome, a concept with profound implications for understanding health and disease. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus.

              Since it was first described in Australia in 1994, Hendra virus (HeV) has caused two outbreaks of fatal disease in horses and humans, and an isolated fatal horse case. Our preliminary studies revealed a high prevalence of neutralizing antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this was due to infection with HeV or a related virus. We developed the hypothesis that HeV excretion from bats might be related to the birthing process and we targeted the reproductive tract for virus isolation. Three virus isolates were obtained from the uterine fluid and a pool of foetal lung and liver from one grey-headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black flying-fox (P. alecto). Antigenically, these isolates appeared to be closely related to HeV, returning positive results on immunofluorescent antibody staining and constant-serum varying-virus neutralization tests. Using an HeV-specific oligonucleotide primer pair, genomic sequences of the isolates were amplified. Sequencing of 200 nucleotides in the matrix gene identified that these three isolates were identical to HeV. Isolations were confirmed after RNA extracted from original material was positive for HeV RNA when screened on an HeV Taqman assay. The isolation of HeV from pteropid bats corroborates our earlier serological and epidemiological evidence that they are a natural reservoir host of the virus.
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                Author and article information

                Contributors
                Journal
                Cell
                Cell
                Cell
                Elsevier Inc.
                0092-8674
                1097-4172
                18 December 2014
                15 January 2015
                18 December 2014
                : 160
                : 1
                : 20-35
                Affiliations
                [1 ]Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID, National Institutes of Health, Bethesda, MD 20892, USA
                [2 ]Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
                [3 ]Sainte-Justine Hospital Research Centre, Department of Pediatrics, University of Montreal, Montreal, QC H3T 1J4, Canada
                [4 ]EcoHealth Alliance, New York, NY 10001, USA
                [5 ]Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
                [6 ]Merck Vaccines, Merck & Co. Inc., West Point, PA 19486, USA
                Author notes
                []Corresponding author mandlj@ 123456niaid.nih.gov
                [7]

                Present address: Department of Physiology and Complex Traits Group, McGill University, Montreal, QC H3G 0B1, Canada

                Article
                S0092-8674(14)01573-6
                10.1016/j.cell.2014.12.003
                4390999
                25533784
                7ea77ed5-2dc4-4cb8-aba7-edc27944b256
                Copyright © 2015 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Cell biology
                Cell biology

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