Modeling HIV-1 Latency in Primary T Cells Using a Replication-Competent Virus
Year: 2015
Type: article
Abstract: HIV-1 latently infected cells in vivo can be found in extremely low frequencies. Therefore, in vitro cell culture models have been used extensively for the study of HIV-1 latency. Often, these in vitro systems utilize defective viruses. Defective viruses allow for synchronized infections and circumvent the use of antiretrovirals. In addition, replication-defective viruses cause minimal cytopathicity because they fail to spread and usually do not encode env or accessory genes. On the other hand, replication-competent viruses encode all or most viral genes and better recapitulate the nuances of the viral replication cycle. The study of latency with replication-competent viruses requires the use of antiretroviral drugs in culture, and this mirrors the use of antiretroviral treatment (ART) in vivo. We describe a model that utilizes cultured central memory CD4(+) T cells and replication-competent HIV-1. This method generates latently infected cells that can be reactivated using latency reversing agents in the presence of antiretroviral drugs. We also describe a method for the removal of productively infected cells prior to viral reactivation, which takes advantage of the downregulation of CD4 by HIV-1, and the use of a GFP-encoding virus for increased throughput.
Institutions: University of Utah, Ghent University
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Bill and Melinda Gates Foundation, Fonds Wetenschappelijk Onderzoek, Vlaamse regering, National Institutes of Health, U.S. Public Health Service, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Center for Advancing Translational Sciences
Awards: G1342889738, University of Utah Center for Clinical and Translational Science, Conservation and Sustainable Use of Biodiversity in PNG, G1852652131, G2488612678, A family of compounds that reactivate latent HIV without T cell activation, G5279787954, Ghent University Hospital - to analyze biomarkers and mRNA transcripts to discover well-defined biomarkers that can be used to assess the extent of the latent HIV reservoir in..., University of Utah Center for clinical and Translational Science, G7076627426, Reactivation of latent HIV through TLR signaling, Martin Delaney Collaboratory to Eradicate HIV-1 Infection
OpenAlex ID: W1690275817