  HIV-1 virions assemble as immature particles containing Gag polyproteins that
are processed by the viral protease into individual components, resulting in
the formation of mature infectious particles. There are two competing models
for the process of forming the mature HIV-1 core: the disassembly and de novo
reassembly model and the non-diffusional displacive model. To study the
maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature
particles and assembled virus-like particles with recombinant HIV-1 protease
and monitor the process with biochemical assays and cryoEM structural analysis
in parallel. Processing of Gag in vitro is accurate and efficient and results
in both soluble capsid protein and conical or tubular capsid assemblies,
seemingly converted from immature Gag particles. Computer simulations further
reveal probable assembly pathways of HIV-1 capsid formation. Combining the
experimental data and computer simulations, our results suggest a sequential
combination of both displacive and disassembly/reassembly processes for HIV-1
maturation.
