Characterization of Barmah Forest virus pathogenesis in a mouse model

Lara HERRERO, Brett Lidbury, Jayaram Bettadapura, Peng Jian, Belinda Herring, William Hey-Cunningham, Kuo-Ching Sheng, Andrew ZAKHARY, Suresh Mahalingam

Research output: Contribution to journalArticle

3 Citations (Scopus)

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-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.
Original languageEnglish
Pages (from-to)2146-2154
Number of pages9
JournalJournal of General Virology
Volume95
Issue number10
DOIs
Publication statusPublished - 2014

Fingerprint

Alphavirus
Ross River virus
Virus Diseases
Arginase
Muscles
Myositis
Tropism

Cite this

HERRERO, L., Lidbury, B., Bettadapura, J., Jian, P., Herring, B., Hey-Cunningham, W., ... Mahalingam, S. (2014). Characterization of Barmah Forest virus pathogenesis in a mouse model. Journal of General Virology, 95(10), 2146-2154. https://doi.org/10.1099/vir.0.064733-0
HERRERO, Lara ; Lidbury, Brett ; Bettadapura, Jayaram ; Jian, Peng ; Herring, Belinda ; Hey-Cunningham, William ; Sheng, Kuo-Ching ; ZAKHARY, Andrew ; Mahalingam, Suresh. / Characterization of Barmah Forest virus pathogenesis in a mouse model. In: Journal of General Virology. 2014 ; Vol. 95, No. 10. pp. 2146-2154.
@article{68f267e4aa054b4e82e247852eca312d,
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-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.",
author = "Lara HERRERO and Brett Lidbury and Jayaram Bettadapura and Peng Jian and Belinda Herring and William Hey-Cunningham and Kuo-Ching Sheng and Andrew ZAKHARY and Suresh Mahalingam",
year = "2014",
doi = "10.1099/vir.0.064733-0",
language = "English",
volume = "95",
pages = "2146--2154",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Society for General Microbiology",
number = "10",

}

HERRERO, L, Lidbury, B, Bettadapura, J, Jian, P, Herring, B, Hey-Cunningham, W, Sheng, K-C, ZAKHARY, A & Mahalingam, S 2014, 'Characterization of Barmah Forest virus pathogenesis in a mouse model', Journal of General Virology, vol. 95, no. 10, pp. 2146-2154. https://doi.org/10.1099/vir.0.064733-0

Characterization of Barmah Forest virus pathogenesis in a mouse model. / HERRERO, Lara; Lidbury, Brett; Bettadapura, Jayaram; Jian, Peng; Herring, Belinda; Hey-Cunningham, William; Sheng, Kuo-Ching; ZAKHARY, Andrew; Mahalingam, Suresh.

In: Journal of General Virology, Vol. 95, No. 10, 2014, p. 2146-2154.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of Barmah Forest virus pathogenesis in a mouse model

AU - HERRERO, Lara

AU - Lidbury, Brett

AU - Bettadapura, Jayaram

AU - Jian, Peng

AU - Herring, Belinda

AU - Hey-Cunningham, William

AU - Sheng, Kuo-Ching

AU - ZAKHARY, Andrew

AU - Mahalingam, Suresh

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907202361&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/characterization-barmah-forest-virus-pathogenesis-mouse-model-3

U2 - 10.1099/vir.0.064733-0

DO - 10.1099/vir.0.064733-0

M3 - Article

VL - 95

SP - 2146

EP - 2154

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 10

ER -

HERRERO L, Lidbury B, Bettadapura J, Jian P, Herring B, Hey-Cunningham W et al. Characterization of Barmah Forest virus pathogenesis in a mouse model. Journal of General Virology. 2014;95(10):2146-2154. https://doi.org/10.1099/vir.0.064733-0