Dataset Information

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4⁺ T Cells From HIV-1 Patients.

ABSTRACT: We described a novel HIV autologous isolation method based in coculturing macrophages and CD4⁺T-cell-enriched fractions from peripheral blood collected from antiretroviral-treated (ART) HIV patients. This method allows the isolation of high viral titers of autologous viruses, over 10¹⁰HIV RNA copies/ml, and reduces the time required to produce necessary amounts for virus for use as antigens presented by monocyte-derived myeloid cells in HIV therapeutic vaccine approaches. By applying these high titer and autologous virus produced in the patient-derived cells, we intended to elicit a boost of the immunological system response in HIV therapeutic vaccines in clinical trials.

SUBMITTER: Xufre C

PROVIDER: S-EPMC9364968 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4+ T Cells From HIV-1 Patients.

Xufré Cristina C González Tanía T Leal Lorna L Trubey Charles M CM Lifson Jeffrey D JD Gatell José María JM Alcamí José J Climent Núria N García Felipe F Sánchez-Palomino Sonsoles S

Frontiers in virology (Lausanne, Switzerland) 20220407

We described a novel HIV autologous isolation method based in coculturing macrophages and CD4+T-cell-enriched fractions from peripheral blood collected from antiretroviral-treated (ART) HIV patients. This method allows the isolation of high viral titers of autologous viruses, over 1010HIV RNA copies/ml, and reduces the time required to produce necessary amounts for virus for use as antigens presented by monocyte-derived myeloid cells in HIV therapeutic vaccine approaches. B ...[more]

PMID: 35967461

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Project description:Future HIV-1 curative therapies require a thorough understanding of the distribution of genetically-intact HIV-1 within T-cell subsets during antiretroviral therapy (ART) and the cellular mechanisms that maintain this reservoir. Therefore, we sequenced near-full-length HIV-1 genomes and identified genetically-intact and genetically-defective genomes from resting naive, stem-cell memory, central memory, transitional memory, effector memory, and terminally-differentiated CD4+ T-cells with known cellular half-lives from 11 participants on ART. We find that a higher infection frequency with any HIV-1 genome was significantly associated with a shorter cellular half-life, such as transitional and effector memory cells. A similar enrichment of genetically-intact provirus was observed in these cells with relatively shorter half-lives. We found that effector memory and terminally-differentiated cells also had significantly higher levels of expansions of genetically-identical sequences, while only transitional and effector memory cells contained genetically-intact proviruses that were part of a cluster of identical sequences. Expansions of identical sequences were used to infer cellular proliferation from clonal expansion. Altogether, this indicates that specific cellular mechanisms such as short half-life and proliferative potential contribute to the persistence of genetically-intact HIV-1. IMPORTANCE The design of future HIV-1 curative therapies requires a more thorough understanding of the distribution of genetically-intact HIV-1 within T-cell subsets as well as the cellular mechanisms that maintain this reservoir. These genetically-intact and presumably replication-competent proviruses make up the latent HIV-1 reservoir. Our investigations into the possible cellular mechanisms maintaining the HIV-1 reservoir in different T-cell subsets have revealed a link between the half-lives of T-cells and the level of proviruses they contain. Taken together, we believe our study shows that more differentiated and proliferative cells, such as transitional and effector memory T-cells, contain the highest levels of genetically-intact proviruses, and the rapid turnover rate of these cells contributes to the expansion of genetically-intact proviruses within them. Therefore, our study delivers an in-depth assessment of the cellular mechanisms, such as cellular proliferation and half-life, that contribute to and maintain the latent HIV-1 reservoir.

Dataset Information

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4⁺ T Cells From HIV-1 Patients.

Publications

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4<sup>+</sup> T Cells From HIV-1 Patients.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4+ T Cells From HIV-1 Patients.

Publications

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4&lt;sup&gt;+&lt;/sup&gt; T Cells From HIV-1 Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4⁺ T Cells From HIV-1 Patients.

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4<sup>+</sup> T Cells From HIV-1 Patients.