HIV-1 transmission: modelling and direct visualization in the third dimension.

Area of Science:

• Virology and Immunology
• Biomedical Engineering
• Organoid Technology

Background:

• Understanding initial human immunodeficiency virus type-1 (HIV-1) mucosal entry is crucial for developing effective transmission-blocking strategies.
• Current models, including 2D cell cultures and animal studies, have limitations in replicating the complex physiological environment of mucosal tissues.
• 2D cultures fail to mimic the niche influencing viral entry, while animal models present challenges in human disease pathophysiology and cost.

Approach:

• This review explores the potential of organoids as a physiologically relevant, high-throughput model for studying HIV-1 mucosal transmission.
• Organoids mimic the biophysical and biochemical niche of mucosal tissues, offering a compromise between 2D cultures and animal models.
• Quantitative light microscopy techniques can be employed to observe events following viral inoculation within organoid models.

Key Points:

• Organoids provide a unique platform to recapitulate key physiological factors of HIV-1 transmission at mucosal sites.
• The review discusses the current limitations of organoid models in HIV-1 research and outlines questions that can be addressed.
• Direct observation of HIV-1 entry in organoids using microscopy can yield significant insights.

Conclusions:

• Harnessing organoids for studying HIV-1 mucosal entry can uncover novel therapeutic targets.
• This approach holds promise for developing strategies to prevent the establishment of HIV-1 infection.
• Organoid technology represents a significant advancement in HIV-1 transmission research.