Death and survival of gut CD4 T cells following HIV-1 infection ex vivo DOI Creative Commons
Kaylee L. Mickens, Stephanie M. Dillon, Kejun Guo

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(11)

Published: Oct. 29, 2024

Abstract The gastrointestinal tract is ground zero for the massive and sustained CD4 T cell depletion during acute HIV-1 infection. To date, molecular mechanisms governing this fundamental pathogenic process remain unclear. infection in associated with chronic inflammation due to a disrupted epithelial barrier that results microbial translocation. Here, we utilized lamina propria aggregate culture model demonstrate profound induction of granzyme B by bacteria primary gut cells ex vivo significantly contributes HIV-1-mediated death. Counterintuitively, substantial fraction B+ harboring high levels survive via pathway linked CD120b/TNFR2. Our findings underscore previously undescribed death survival could inform strategies counter pathogenesis persistence critical tissue compartment.

Language: Английский

Current status of mannose receptor-targeted drug delivery for improved anti-HIV therapy DOI
Satish Rojekar, Amol D. Gholap, Namdev Togre

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 494 - 521

Published: June 27, 2024

Language: Английский

Citations

14
CUL4-Based Ubiquitin Ligases in Chromatin Regulation: An Evolutionary Perspective DOI Creative Commons

Makiko Nakagawa,

Tadashi Nakagawa

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 63 - 63

Published: Jan. 7, 2025

Ubiquitylation is a post-translational modification that modulates protein function and stability. It orchestrated by the concerted action of three types enzymes, with substrate specificity governed ubiquitin ligases (E3s), which may exist as single proteins or part multi-protein complexes. Although Cullin (CUL) lack intrinsic enzymatic activity, they participate in formation active ligase complexes, known Cullin-Ring Ligases (CRLs), through their association ROC1 ROC2, along adaptor receptor proteins. Mammalian genomes encode several CUL (CUL1-9), each contributing to distinct CRLs. Among these proteins, CUL1, CUL3, CUL4 are believed be most ancient evolutionarily conserved from yeast mammals, uniquely duplicated vertebrates. Genetic evidence strongly implicates CUL4-based (CRL4s) chromatin regulation across various species suggests that, vertebrates, CRL4s have also acquired cytosolic role, facilitated cytosol-localizing paralog CUL4. Substrates identified biochemical studies elucidated molecular mechanisms regulate processes. The substantial body knowledge on biology amassed over past two decades provides unique opportunity explore functional evolution CRL4. In this review, we synthesize available structural, genetic, data CRL4 model organisms discuss novel functions CRL4s.

Language: Английский

Citations

1
CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X DOI Creative Commons

Ashley Dobransky,

Mary Root,

Nicholas Hafner

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1313 - 1313

Published: Aug. 17, 2024

The Human Immunodeficiency Virus (HIV) encodes several proteins that contort the host cell environment to promote viral replication and spread. This is often accomplished through hijacking of cellular ubiquitin ligases. These reprogrammed complexes initiate or enhance ubiquitination may otherwise act restrain replication. Ubiquitination target alter protein function proteasome-dependent destruction. HIV Viral Protein R (Vpr) related HIV-2 X (Vpx), engage CRL4-DCAF1 ligase complex numerous proteins. In this review we describe its interactions with Vpr Vpx. We additionally summarize targeted by association as well observed hypothesized impact on HIV.

Language: Английский

Citations

2
Interferon-Regulated Expression of Cellular Splicing Factors Modulates Multiple Levels of HIV-1 Gene Expression and Replication DOI Creative Commons
Fabian Roesmann, Lisa Müller,

Katleen Klaassen

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 938 - 938

Published: June 11, 2024

Type I interferons (IFN-Is) are pivotal in innate immunity against human immunodeficiency virus (HIV-1) by eliciting the expression of IFN-stimulated genes (ISGs), which encompass potent host restriction factors. While ISGs restrict viral replication within cell targeting various stages life cycle, lesser-known IFN-repressed (IRepGs), including RNA-binding proteins (RBPs), affect altering dependency factors that essential for efficient HIV-1 gene expression. Both and determine efficiency; however, understanding IRepGs implicated infection remains greatly limited at present. This review provides a comprehensive overview current regarding impact protein families, specifically two families splicing-associated SRSF hnRNP, on replication. Since recent findings show SRSF1 hnRNP A0 regulated IFN-I lines primary cells, intestinal lamina propria mononuclear cells (LPMCs) peripheral blood (PBMCs), we particularly discuss their role context affecting

Language: Английский

Citations

0
The HIV-1 vpr R77Q Mutant Induces Apoptosis, G2 Cell Cycle Arrest, and Lower Production of Pro-Inflammatory Cytokines in Human CD4+ T Cells DOI Creative Commons
Antonio Solis‐Leal, Dalton C. Karlinsey,

Sidney T. Sithole

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1642 - 1642

Published: Oct. 21, 2024

Acquired immunodeficiency syndrome (AIDS) occurs when HIV depletes CD4+ helper T cells. Some patients develop AIDS slowly or not at all, and are termed long-term non-progressors (LTNP), while mutations in the HIV-1 Viral Protein R (

Language: Английский

Citations

0
Death and survival of gut CD4 T cells following HIV-1 infection ex vivo DOI Creative Commons
Kaylee L. Mickens, Stephanie M. Dillon, Kejun Guo

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(11)

Published: Oct. 29, 2024

Abstract The gastrointestinal tract is ground zero for the massive and sustained CD4 T cell depletion during acute HIV-1 infection. To date, molecular mechanisms governing this fundamental pathogenic process remain unclear. infection in associated with chronic inflammation due to a disrupted epithelial barrier that results microbial translocation. Here, we utilized lamina propria aggregate culture model demonstrate profound induction of granzyme B by bacteria primary gut cells ex vivo significantly contributes HIV-1-mediated death. Counterintuitively, substantial fraction B+ harboring high levels survive via pathway linked CD120b/TNFR2. Our findings underscore previously undescribed death survival could inform strategies counter pathogenesis persistence critical tissue compartment.

Language: Английский

Citations

0