Dengue Virus AG129 Mouse Model

This unique lethal model uses a non-mouse-adapted strain of DENV serotype 2 (D2Y98P), isolated from a DENV-infected patient in Singapore, which is highly infectious in AG129 mice.

The model provides consistent clinical manifestations of disease similar to those observed in human cases as previously described.


Advantages of the model:

  • Low dose of virus required to lead to transient asymptomatic infection followed by death a few days after viral clearance, similar to the progression of the disease in humans.
  • Increased vascular permeability without morphological damage of the capillary endothelium similar to human disease.
  • Three key pro-inflammatory cytokines implicated in Dengue Hemorrhagic Fever (DHF) are significantly elevated in D2Y98P-infected AG129 mice.

Other animal models of dengue

Non-human primates frequently do not exhibit clinical symptoms of the disease thereby limiting their usefulness for product development. Other mouse models of DENV exist but face challenges because most DENV laboratory strains and clinical isolates do not replicate efficiently in mice. Mouse-adapted DENV strains can display higher infectivity but can lead to irrelevant clinical manifestations such as paralysis. Mice deficient in interferon IFN α/β and γ receptors (AG129 mice) have been shown to allow effective replication of DENV.

Fig. 1 Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain). Inoculum 1xLD90=1.0E+05 PFU/mouse
Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain) 1.0E+05 PFU/mouse
Survival and weight change in BALB/c mice challenged with INFV A/ Texas/36/91 (H1N1) and treated with antiviral Osletamivir Phosphate (Tamiflu)
Lung viral load and Survival (30 % weight loss cut-off) in BALB/c mice challenged with INFV H3N2 A/HK/1/68.

Alpha (UK) – B. 1.1.7 / 501Y.V1

amino acid mutations: del69–70 HV, del144 Y, N501Y, A570D, D614G, P681H, T761I, S982A, D1118H

Beta (South Africa) – B.1.351

amino acid mutations: K417N, E484K, N501Y, D614G, A701V

Gamma (Brazil) – P.1

amino acid mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I

Epsilon (Ca, USA) B.1.427

amino acid mutations: L452R, D614G

SARS-CoV-2 Parental Strain Wild Type (Wuhan)
SARS-CoV-2 D614G Variant

amino acid mutations: D614G

Epsilon (Ca, USA) B.1.429

amino acid mutations: S13I, W152C, L452R, D614G

SARS-CoV-2 Delta Variant

amino acid mutations: L452R, E484Q