From HIV infection to AIDS: a dynamically induced percolation transition?

Area of Science:

• Immunology
• Virology
• Computational Biology

Background:

• The incubation period distribution for Acquired Immunodeficiency Syndrome (AIDS) is not fully understood.
• The dynamics between the Human Immunodeficiency Virus (HIV) and the immune system are crucial for understanding latency and non-progression.
• Depletion of CD4+ cells by HIV weakens the immune system over time.

Purpose of the Study:

• To investigate the factors contributing to the unusual incubation period distribution in AIDS development.
• To model the interplay between viral genome diversification and immune system pressure.
• To explain the existence of individuals who do not develop AIDS (non-progressors).

Main Methods:

• Utilized computer simulations to model viral genome diversification under mutation.
• Incorporated the selective pressure of the immune system into the model.
• Analyzed the dynamics within a sequence space framework, including a dynamically induced percolation transition.

Main Results:

• HIV infection leads to significant viral genome spreading in genome space, unlike other infections.
• A dynamically induced percolation transition in sequence space correlates with AIDS onset.
• The model successfully reproduces a prolonged incubation period distribution and a fraction of non-progressors.

Conclusions:

• HIV's ability to weaken the immune system drives extensive viral genome diversification.
• This diversification and immune depletion trigger a transition leading to AIDS.
• The simulation results align with clinical observations of AIDS incubation periods and non-progression rates.