Modeling the effects of HIV-1 virions and proteins on Fas-induced apoptosis of infected cells

TL;DR

This paper presents a novel computational model simulating how HIV-1 proteins influence Fas-mediated apoptosis in infected T cells, providing new insights into the lifespan of reactivated latent HIV-infected cells.

Contribution

It introduces the first detailed simulation of HIV effects on the Fas apoptotic pathway in infected memory T cells, integrating literature data and experimental fitting.

Findings

Estimated lifetime of reactivated latent T cells is about 42 hours.

First modeling study of HIV impact on Fas-induced apoptosis in infected cells.

Provides a basis for future HIV cure strategies targeting infected T cell apoptosis.

Abstract

We report a first in modeling and simulation of the effects of the HIV proteins on the (caspase dependent) apoptotic pathway in infected cells. This work is novel and is an extension on the recent reports and clarifications on the FAS apoptotic pathway from the literature. We have gathered most of the reaction rates and initial conditions from the literature, the rest of the constants have been computed by fitting our model to the experimental results reported. Using the model obtained we have then run the simulations for the infected memory T cells, called also latent T cells, which, at the moment, represent the major obstacle to finding a cure for HIV. We can now report that the infected latent T cells have an estimated lifetime of about 42 hours from the moment they are re-activated. As far as we know this is the first result of this type obtained for the infected memory T cells.