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  • Characterization of Barmah Forest virus (BFV) pathogenesis in a mouse model

    Author(s)
    Herrero, Lara J
    Lidbury, Brett A
    Bettadapura, Jayaram
    Jian, Peng
    Herring, Belinda L
    Hey-Cunningham, William J
    Sheng, Kuo-Ching
    Zakhary, Andrew
    Mahalingam, Suresh
    Griffith University Author(s)
    Mahalingam, Suresh
    Bettadapura, Jayaram
    Jian, Jian
    Herrero, Lara J.
    Sheng, Kuo-Ching
    Herring, Belinda
    Year published
    2014
    Metadata
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    Abstract
    Alphaviruses including Barmah Forest virus (BFV) and Ross River virus (RRV) cause arthritis, arthralgia and myalgia in humans. The rheumatic symptoms in human BFV infection are very similar to those of RRV. Although RRV disease has been studied extensively, little is known about the pathogenesis of BFV infection. We sought to establish a mouse model for BFV to facilitate our understanding of BFV infectivity, tropism and pathogenesis, and to identify key pathological and immunological mechanisms of BFV infection that may distinguish between infections with BFV and RRV. Here, to the best of our knowledge, we report the first ...
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    Alphaviruses including Barmah Forest virus (BFV) and Ross River virus (RRV) cause arthritis, arthralgia and myalgia in humans. The rheumatic symptoms in human BFV infection are very similar to those of RRV. Although RRV disease has been studied extensively, little is known about the pathogenesis of BFV infection. We sought to establish a mouse model for BFV to facilitate our understanding of BFV infectivity, tropism and pathogenesis, and to identify key pathological and immunological mechanisms of BFV infection that may distinguish between infections with BFV and RRV. Here, to the best of our knowledge, we report the first study assessing the virulence and replication of several BFV isolates in a mouse model. We infected newborn Swiss outbred mice with BFV and established that the BFV2193 prototype was the most virulent strain. BFV2193 infection resulted in the highest mortality among all BFV variant isolates, comparable to that of RRV. In comparison with RRV, C57BL/6 mice infected with BFV showed delayed onset, moderate disease scores and early recovery of the disease. BFV replicated poorly in muscle and did not cause the severe myositis seen in RRV-infected mice. The mRNAs for the inflammatory mediators TNF-a, IL-6, CCL2 and arginase-1 were highly upregulated in RRV- but not BFV-infected muscle. To our knowledge, this is the first report of a mouse model of BFV infection, which we have used to demonstrate differences between BFV and RRV infections and to further understand disease pathogenesis. With an increasing number of BFV cases occurring annually, a better understanding of the disease mechanisms is essential for future therapeutic development.
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    Journal Title
    Journal of General Virology
    Volume
    95
    DOI
    https://doi.org/10.1099/vir.0.064733-0
    Subject
    Biological sciences
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Medical virology
    Publication URI
    http://hdl.handle.net/10072/64870
    Collection
    • Journal articles

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