Development of a transmission model for dengue virus

Area of Science:

• Virology
• Immunology
• Entomology

Background:

• Dengue virus (DENV) research has been limited by the absence of a susceptible vertebrate transmission model.
• Type I interferon responses are crucial in limiting DENV infection.
• Previous models utilized knockout mice deficient in interferon receptors.

Purpose of the Study:

• To assess the permissiveness of a mouse strain deficient in interferon regulatory factors 3 and 7 (IRF3/7 -/- -/-) for DENV transmission.
• To investigate DENV transmission to mice via needle and mosquito.
• To evaluate subsequent transmission from infected mice back to mosquitoes.

Main Methods:

• Mice were inoculated with a non-mouse adapted DENV-2 strain.
• Serum viral load and cytokine production were monitored daily.
• Mosquitoes were orally challenged and then allowed to feed on mice, or vice versa, to assess transmission and acquisition potentials.

Main Results:

• 100% infection rates were achieved through both needle inoculation and infectious mosquito bites.
• The IRF3/7 -/- -/- mouse model supported DENV replication and transmission.
• The complete DENV transmission cycle (mouse-to-mosquito-to-mouse) was successfully established.

Conclusions:

• The IRF3/7 -/- -/- mouse is a competent model for DENV transmission studies.
• This model allows for the use of non-mouse adapted DENV strains.
• Understanding DENV transmission dynamics is critical for public health monitoring and outbreak prevention.