Quantitative intracellular kinetics of HIV type 1

Although our knowledge of HIV-1 growth, from a molecular mechanistic perspe ctive, has rapidly increased, we do not yet know how the overall growth rat e of HIV-1 depends on its constituent biochemical reactions. Such an unders tanding would be of fundamental importance and potentially useful for desig ning and evaluating anti-HIV strategies. As a first step toward addressing this need we formulate and implement here a global computer simulation for the intracellular growth of HIV-1 on a CD4(+) T lymphocyte. Our simulation accounts for the kinetics of reverse transcription, integration of proviral DNA into the host genome, transcription, mRNA splicing and transport from the nucleus, translation, feedback of regulatory proteins to the nucleus, t ransport of viral proteins to the cell membrane, particle assembly, budding , and maturation. The simulation quantitatively captures the experimentally observed intracellular dynamics of viral DNA, mRNA, and proteins while emp loying no "fudge factors." Moreover, it provides an estimate of the intrace llular growth rate of HIV-1 and enables evaluation of mono- and combined an ti-HIV strategies.