title: Characterization of Barmah Forest virus pathogenesis in a mouse model.
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 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-α, 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.
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.affiliation: School of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT 0200, Australia.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Lidbury
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Jayaram
authors.initials: J
authors.lastname: Bettadapura
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Peng
authors.initials: P
authors.lastname: Jian
authors.affiliation: Department of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.|Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Belinda L
authors.initials: BL
authors.lastname: Herring
authors.affiliation: Department of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hey-Cunningham
authors.affiliation: Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zakhary
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D000524:Alphavirus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D018354:Alphavirus Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014774:Virulence; D014779:Virus Replication
chemical_list: D016207:Cytokines