Mucosal administration of low-dose cell-associated feline immunodeficiency virus promotes viral latency

Area of Science:

• Virology
• Immunology
• Animal Models

Background:

• Human immunodeficiency virus type 1 (HIV-1) can establish latent infections in asymptomatic individuals.
• Understanding latent viral reservoirs is crucial for developing effective treatment strategies.
• Existing animal models may not fully replicate the complexities of HIV-1 latency.

Purpose of the Study:

• To establish a novel animal model for studying host-controlled viral latency.
• To investigate the induction and reactivation of latent feline immunodeficiency virus (FIV) infection.
• To explore mechanisms controlling the establishment of viral reservoirs.

Main Methods:

• Cats were mucosally challenged with varying doses of FIV-infected T cells.
• High-dose and low-dose exposure groups were established to assess infection outcomes.
• Ex vivo CD8(+) T cell depletion and phorbol myristate acetate treatment were used to attempt viral reactivation.

Main Results:

• High-dose FIV exposure led to progressive infection in cats.
• Low-dose FIV exposure (10^2-10^3 T cells) resulted in apparent non-infection in most cats.
• FIV reactivation was achieved in tissues of 4 out of 5 cats from the low-dose group after specific ex vivo treatments.
• This indicates the successful induction of latent tissue viral reservoirs.

Conclusions:

• Low-dose, cell-associated mucosal challenge can induce latent FIV reservoirs in cats.
• This feline model provides a platform for dissecting the mechanisms of viral reservoir establishment and control.
• Further research using this model can inform strategies against persistent viral infections like HIV-1.