title: LGIT In Vitro Latency Model in Primary and T Cell Lines to Test HIV-1 Reactivation Compounds.
abstract: Persistent latent HIV-1 reservoirs pose a major barrier for combinatorial antiretroviral therapy (cART) to achieve eradication of the virus. A variety of mechanisms likely contribute to HIV-1 persistence, including establishment of post-integration latency in resting CD4+ T-lymphocytes, the proliferation of these latently infected cells, and the induced or spontaneous reactivation of latent virus. To elucidate the mechanisms of latency and to investigate therapeutic strategies for reactivating and purging the latent reservoir, investigators have developed in vitro models of HIV-1 latency using primary CD4+ T-lymphocytes and CD4+ T-cell lines. Several types of in vitro latency models range from replication-competent to single-round, replication-deficient viruses exhibiting different degrees of viral genomic deletion. Working under the hypothesis that HIV-1 post-integration latency is directly linked to HIV-1 promoter activity, which can be obscured by additional proteins expressed during replication, we focus here on the creation of latently infected primary human T-cells and cell lines through the single-round, replication deficient HIV-1 LGIT model. In this model the long terminal repeat (LTR) of the HIV-1 virus drives a cassette of GFP-IRES-Tat that allows testing of reactivating components and initiates a positive feedback loop through Tat expression.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Jung
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.|Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Fox North, 1001A, 1500 Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. jburnett@coh.org.|Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Fox North, 1001A, 1500 Duarte Rd., Duarte, CA, 91010, USA. jburnett@coh.org.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D005434:Flow Cytometry / Q000379:methods; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents
keywords: HIV; LGIT; LTR; Latency; Primary T-cells; Reactivation; T-cell line