A model for continuously mutant HIV-1

Horacio Ortega, Miguel Martin-Landrove

 

Proceedings of the 22"d Annual EMBS International Conference, July 23-28,2000, Chicago IL.

 

In this model we use the immunodominance concept introduced by Nowak et a& (1995) for explaining variations in the immune response induced against virus having mutant epitopes. We propose as source of free virions, mononuclear peripheral blood cells such as macrophages, in addition to the currently accepted one, the T-CD4 cells. Our model suppose healthy and infected reservoirs, virions, T-helper and cytotoxic cells. Reservoirs after infected by virus, and exhibit viral epitopes. They are attacked by cytotoxic cells addressed against those epitopes seen by the immune system. We also propose extra cellular T-helper cell coordinated attack against free virions. We begin studying just one viral variant, and after making some approximations, we find a stability criterion that allows differentiating control from viral outgrowth. When analyzing the system without any approximation, we find no analytical solution, but numerical simulations show that a) the precedent criterion is, however, useful, in determining the system evolution, and b) cytotoxic cell attack against reservoirs is a powerful resource in viral control. We then generalize our model to situations with N epitopes, each one with M viral variants (for simulations N=M=2), and we use a Metropolis-like algorithm for generating viral variants. Viral mutability and number of viral variants are related to viral progression. Our results suggest that it is important to include in the therapy control mechanisms for avoiding viral invasion and proliferation inside reservoirs. Until this goal is achieved avoiding infection is the only safe measure against AIDS.