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Mathematical modeling and quantitative analysis of HIV-1 Gag trafficking and polymerization.
- Source :
-
PLoS Computational Biology . 9/18/2017, Vol. 13 Issue 9, p1-27. 27p. 2 Color Photographs, 7 Charts, 10 Graphs. - Publication Year :
- 2017
-
Abstract
- Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed. Using our model, we analyzed the weight of the pathways involved in the polymerization reactions and concluded that the predominant pathways for the formation of a hexamer might be the polymerization of two monomers to form a dimer, the polymerization of a dimer and a monomer to form a trimer, and the polymerization of two trimers to form a hexamer. We then deduced that the dimer and trimer intermediates might be crucial in hexamer formation. We also explored four theoretical combined methods for Gag suppression, and hypothesized that the N-terminal glycine residue of the MA domain of Gag might be a promising drug target. This work serves as a guide for future theoretical and experimental efforts aiming to understand HIV-1 Gag trafficking and polymerization, and might help accelerate the efficiency of anti-AIDS drug design. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1553734X
- Volume :
- 13
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- PLoS Computational Biology
- Publication Type :
- Academic Journal
- Accession number :
- 125204679
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1005733