As knowledge of individual biological processes grows, it becomes increasingly useful to frame new findings within their larger biological contexts in order to generate new systems-scale hypotheses. This report highlights two major iterations of a whole virus model of HIV-1, generated with the cellPACK software. cellPACK integrates structural and systems biology data with packing algorithms to assemble comprehensive 3D models of cell-scale structures in molecular detail. This report describes the biological data, modeling parameters and cellPACK methods used to specify and construct editable models for HIV-1. Anticipating that cellPACK interfaces under development will enable researchers from diverse backgrounds to critique and improve the biological models, we discuss how cellPACK can be used as a framework to unify different types of data across all scales of biology.
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http://dx.doi.org/10.1039/c4fd00017j | DOI Listing |
PLoS Pathog
December 2024
Amsterdam UMC, location University of Amsterdam, Experimental Immunology, Amsterdam, The Netherlands.
The gastrointestinal tract is a prominent portal of entry for HIV-1 during sexual or perinatal transmission, as well as a major site of HIV-1 persistence and replication. Elucidation of underlying mechanisms of intestinal HIV-1 infection are thus needed for the advancement of HIV-1 curative therapies. Here, we present a human 2D intestinal immuno-organoid system to model HIV-1 disease that recapitulates tissue compartmentalization and epithelial-immune cellular interactions.
View Article and Find Full Text PDFJ Virol
December 2024
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Previous studies have shown that the majority of long-lived cells harboring persistent HIV-1 proviral genomes originates from viruses circulating in the year prior to antiretroviral therapy (ART) initiation, but a smaller proportion originates from viruses circulating much earlier in untreated infection. These observations suggest that discrete biological factors influence the entry and persistence of viruses into the persistent proviral pool, and there may be periods earlier in untreated infection with increased seeding. Therefore, we examined the timing of formation of the long-lived pool of infected cells that persists during ART in seven women (after a median of 5.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Department of Synthesis and Technology of Drugs, Medical University of Białystok, Kilińskiego 1, 15-089 Białystok, Poland.
Many pathogens including viruses enter cells by endocytosis. We identified and evaluated novel endocytosis inhibitors capable of blocking the entry of the HIV-1 Tat protein into neuronal cells and investigated their potential protective properties against Tat-induced neurotoxicity. In this study, the compounds Les-6631 and Les-6633 were synthesized and assessed.
View Article and Find Full Text PDFMol Neurobiol
December 2024
NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong District, Kunming, 650500, China.
Co-exposure to methamphetamine (METH) abuse and HIV infection exacerbates central nervous system damage. However, the underlying mechanisms of this process remain poorly understood. This study aims to explore the roles of neuronal autophagy in the synergistic damage to the central nervous system caused by METH and HIV proteins.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.
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