Poster abstracts
Poster number 109 submitted by Ioulia Rouzina
Kinetic selectivity of viral genome packaging by HIV-1
Ioulia Rouzina (Biochemistry, OSU), Orlando Guzman (Departamento de Fsica, Universidad Autnoma Metropolitana, Iztapalapa, Ciudad de Mxico, Mxico), Robijn Bruinsma (University of California, Los Angeles, UCLA Department of Physics and Astronomy, Los Angeles, CA)
Abstract:
Over 90% of virions released from the HIV-1 infected cells contain viral genomic RNA (gRNA) dimers. How HIV-1 (and other retroviruses) accomplish this high selectivity remains a mystery, as cytoplasm of the infected cell has over 1000-fold excess of the host mRNAs that can also support assembly of similar virions. This highly selective gRNA packaging cannot be explained by the modest Gag protein binding preference for the gRNA packaging signal - Psi. In this theoretical work we bring together a large body of experimental data to build a model of kinetic gRNA packaging. We propose that gRNA gets selectively packaged because it facilitates faster virion assembly than non-gRNA. This mechanism works best when the virion assembly is slow, which is the case for the HIV-1 infected cells with low rates of gRNA and Gag synthesis. The main contribution to faster assembly on gRNA vs mRNA comes from the longer gRNA length, allowing continuous Gag cluster growth on PM and virion assembly completion on a single gRNA dimer. In contrast, Gag clusters assembling on mRNAs are two small to make the whole virion and need to fuse together on PM to complete the assembly. This is a slower process, leading to most of the virions completing the assembly with gRNA, i. e. to its selective packaging. We describe kinetics of virion nucleation and growth, and of the Gag clusters fusion on PM coupled to the Gag exchange in the cell as it is synthesized in the cytoplasm and released in the form of virions. Our theory allows to predict dependence of the gRNA dimer packaging selectivity on properties of gRNA: its specificity for Gag, its dimerization propensity and its length. We also make novel predictions for the selectivity dependence on: Gag synthesis rate, Gag-Gag interaction free energy, strength of MA attachment to PM, rate of Gag clusters diffusion on PM, total number of VLP assembly sites on PM of the cell.
Keywords: HIV, genome, packaging