Generation and evaluation of an EcoHIV mouse model to study HIV-1 integration and expression

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Antiretroviral therapy (ART) controls HIV replication but cannot eliminate latent viral reservoirs, hindering a cure.
• A suitable animal model is crucial for studying HIV latency, viral dynamics, and developing clearance strategies.

Purpose of the Study:

• To establish and validate a novel mouse model (EcoHIV) for investigating HIV latency and evaluating potential curative interventions.
• To assess viral entry, integration, transmission, and latency establishment in a controlled preclinical setting.

Main Methods:

• Developed an EcoHIV model using a modified HIV-1 envelope for entry via murine receptors.
• Validated a nested qPCR assay for quantifying HIV-1/EcoHIV integration events.
• Utilized immunofluorescence and BLI (bioluminescence imaging) to track viral transmission, expression, and latency.

Main Results:

• EcoHIV successfully infected immunocompetent mice and various immune cells, including CD4+ T cells and macrophages.
• HIV integrase inhibitors (e.g., Raltegravir) significantly suppressed viral integration.
• EcoHIV demonstrated efficient cell-to-cell transmission and established latent reservoirs reactivatable by latency-reversing agents (LRAs).

Conclusions:

• The EcoHIV mouse model provides a valuable platform for studying HIV pathogenesis, including entry, integration, transmission, and latency.
• This model facilitates the preclinical evaluation of ART, latency-reversing therapies, and potential HIV cure strategies.