Antigen-driven clonal selection shapes the persistence of HIV-1-infected CD4+ T cells in vivo.

Clonal expansion of infected CD4+ T cells is a major mechanism of HIV-1 persistence and a barrier to achieving a cure. Potential causes are homeostatic proliferation, effects of HIV-1 integration, and interaction with antigens. Here, we show that it is possible to link antigen responsiveness, the full proviral sequence, the integration site, and the T cell receptor β-chain (TCRβ) sequence to examine the role of recurrent antigenic exposure in maintaining the HIV-1 reservoir.

Similar Frequency and Inducibility of Intact Human Immunodeficiency Virus-1 Proviruses in Blood and Lymph Nodes.

Background: The human immunodeficiency virus (HIV)-1 latent reservoir (LR) in resting CD4+ T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes.

Methods: We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from 10 HIV-1-infected patients on antiretroviral therapy (ART) using the intact proviral DNA assay and a novel quantitative viral induction assay.

Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda.

HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbors integrated provirus within host cellular DNA. Increasing evidence links sex-based differences in HIV-1 immune responses and pathogenesis; however, little is known about differences in HIV-1 infection persistence. Here, we quantified persistent HIV-1 infection in 90 adults on suppressive antiretroviral therapy in Rakai, Uganda (57 female patients).

Different human resting memory CD4 T cell subsets show similar low inducibility of latent HIV-1 proviruses.

The latent reservoir of HIV-1 in resting CD4 T cells is a major barrier to cure. It is unclear whether the latent reservoir resides principally in particular subsets of CD4 T cells, a finding that would have implications for understanding its stability and developing curative therapies. Recent work has shown that proliferation of HIV-1-infected CD4 T cells is a major factor in the generation and persistence of the latent reservoir and that latently infected T cells that have clonally expanded in vivo can proliferate in vitro without producing virions.

A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4 T cells is the principal barrier to a cure. Curative strategies that target the reservoir are being tested and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation.

Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane.

The latent reservoir for HIV-1 in resting CD4 T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses.

HIV persistence: clonal expansion of cells in the latent reservoir.

While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al.

Proliferation of latently infected CD4 T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics.

A latent reservoir for HIV-1 in resting CD4 T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence.

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative.

A pangenomic analysis of the Nannochloropsis organellar genomes reveals novel genetic variations in key metabolic genes.

Background: Microalgae in the genus Nannochloropsis are photosynthetic marine Eustigmatophytes of significant interest to the bioenergy and aquaculture sectors due to their ability to efficiently accumulate biomass and lipids for utilization in renewable transportation fuels, aquaculture feed, and other useful bioproducts. To better understand the genetic complement that drives the metabolic processes of these organisms, we present the assembly and comparative pangenomic analysis of the chloroplast and mitochondrial genomes from Nannochloropsis salina CCMP1776.

Results: The chloroplast and mitochondrial genomes of N.