A dengue virus type 4 model of disseminated lethal infection in AG129 mice

Gregg Milligan, Vanessa Sarathy, Ernesto Infante, Li Li, Gerald Campbell, P. Robert Beatty, Eva Harris, Alan Barrett, Nigel Bourne

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals.

Original languageEnglish (US)
Article numbere0125476
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 4 2015

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Dengue virus
Dengue Virus
Viruses
dengue
Dengue
mice
Infection
infection
human diseases
Animals
serotypes
animal models
mosquito-borne diseases
vaccines
Antiviral Agents
interferon-alpha
disease models
thrombocytopenia
Vaccines
large intestine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A dengue virus type 4 model of disseminated lethal infection in AG129 mice. / Milligan, Gregg; Sarathy, Vanessa; Infante, Ernesto; Li, Li; Campbell, Gerald; Beatty, P. Robert; Harris, Eva; Barrett, Alan; Bourne, Nigel.

In: PLoS One, Vol. 10, No. 5, e0125476, 04.05.2015.

Research output: Contribution to journalArticle

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