HIV-1 and Compromised Adult Neurogenesis: Emerging Evidence for a New Paradigm of HAND Persistence DOI

Raj Putatunda,

Wen‐Zhe Ho,

Wenhui Hu

et al.

Aids Reviews, Journal Year: 2019, Volume and Issue: 21(1)

Published: March 18, 2019

The face of the HIV-1/AIDS pandemic has changed significantly thanks to development antiretroviral therapy (ART) regimens. Unfortunately, several HIV-associated comorbidities continuously occur in clinical population, most notably neurocognitive disorders (HAND). While many molecular and cellular mechanisms have been characterized by describing HAND pathology (specifically neuroinflammatory insults oxidative stress) ART era, compromised adult neurogenesis is emerging as a potential new mechanism. Neurogenesis dynamic process that generates neurons glial cells from neural stem (NSCs) progenitor (NPCs) specific areas brain. There are increasing observations HIV-1 can productively non-productively infect NSCs NPCs. proteins and/or secondary immune/inflammatory responses impair initial differentiation NPCs, restrict neuronal lineage differentiation, aberrantly promote astrocytic differentiation. Recent studies with transgenic animal models demonstrate varying degrees neurogenic deficits, which correlate milder moderate forms impairments. dysfunction underlying highlights importance developing therapeutics restore homeostasis patients.

Language: Английский

HIV-1 capsid: the multifaceted key player in HIV-1 infection DOI
Edward M. Campbell, Thomas J. Hope

Nature Reviews Microbiology, Journal Year: 2015, Volume and Issue: 13(8), P. 471 - 483

Published: July 16, 2015

Language: Английский

Citations

392
Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4+ T Cells and Offers an Opportunity to Tackle Infection DOI Creative Commons
José Carlos Valle‐Casuso, Mathieu Angin,

Stevenn Volant

et al.

Cell Metabolism, Journal Year: 2018, Volume and Issue: 29(3), P. 611 - 626.e5

Published: Dec. 20, 2018

Language: Английский

Citations

161
Innate and intrinsic antiviral immunity in Drosophila DOI

Assel Mussabekova,

Laurent Daeffler, Jean‐Luc Imler

et al.

Cellular and Molecular Life Sciences, Journal Year: 2017, Volume and Issue: 74(11), P. 2039 - 2054

Published: Jan. 19, 2017

Language: Английский

Citations

125
Programming cytomegalovirus as an HIV vaccine DOI Creative Commons
Louis J. Picker, Jeffrey D. Lifson, Michael Gale

et al.

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(4), P. 287 - 304

Published: March 7, 2023

The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8+ T cells in tissues immediate immune interception nascent primary infection. This goal achieved and also led the unexpected discoveries that non-human primate (NHP) CMVs can be programmed differentially elicit cell responses recognize viral peptides via classical MHC-Ia, and/or MHC-II, MHC-E, MHC-E-restricted uniquely mediate stringent arrest subsequent clearance highly pathogenic SIV, an unprecedented type vaccine-mediated protection. These delineate CMV vector-elicited functionally distinct response with superior efficacy against HIV-1, possibly other infectious agents or cancers.

Language: Английский

Citations

34
FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking DOI Creative Commons
P. J. Huang, Brady J. Summers, Chaoyi Xu

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 28(9), P. 2373 - 2385.e7

Published: Aug. 1, 2019

HIV-1 uses the microtubule network to traffic viral capsid core toward nucleus. Viral nuclear trafficking and infectivity require kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with specifically binds (CA) hexamers. contains multiple acidic, poly-glutamate stretches interact positively charged central pore of CA The FEZ1-capsid interaction competes nucleotides inositol hexaphosphate (IP6) bind at same location. In addition, all-atom molecular dynamic (MD) simulations establish details interactions. Functionally, mutation capsid-interacting residues significantly reduces particles nucleus early infection. These findings support a model in which hexamer is general cofactor-binding hub serves as unique pattern sensor recognize this site promote cell.

Language: Английский

Citations

72
Cullin-RING E3 Ubiquitin Ligases: Bridges to Destruction DOI
Henry C. Nguyen, Wei Wang, Yong Xiong

et al.

Sub-cellular biochemistry/Subcellular biochemistry, Journal Year: 2017, Volume and Issue: unknown, P. 323 - 347

Published: Jan. 1, 2017

Language: Английский

Citations

67
Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation DOI Creative Commons
Hashim Ali, Miguel Mano, Luca Braga

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Feb. 25, 2019

Abstract Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of the genome into host cell DNA. IN, however, is short lived and rapidly degraded by ubiquitin-proteasome system. To identify cellular factors responsible for IN degradation, we performed a targeted RNAi screen using library siRNAs against all components ubiquitin-conjugation machinery high-content microscopy. Here report that E3 RING ligase TRIM33 major determinant stability. CD4-positive cells with knock down show increased proviral DNA formation, while those overexpressing factor display opposite effects. Knock reverts phenotype an molecular clone carrying substitution serine 57 to alanine, mutation known impair integration. Thus, acts as restricting infection preventing provirus formation.

Language: Английский

Citations

59
Mechanism of Viral Glycoprotein Targeting by Membrane-Associated RING-CH Proteins DOI Creative Commons
Cheng Man Lun, Abdul Waheed,

Ahlam Majadly

et al.

mBio, Journal Year: 2021, Volume and Issue: 12(2)

Published: March 15, 2021

Viral envelope glycoproteins are an important structural component on the surfaces of enveloped viruses that direct virus binding and entry also serve as targets for host adaptive immune response. In this study, we investigate mechanism action MARCH family cellular proteins disrupt trafficking virion incorporation viral across several families.

Language: Английский

Citations

42
Macrophage membrane-coated nanoparticles for the treatment of infectious diseases DOI
Chenguang Wang,

Chuyu Li,

Ruoyu Zhang

et al.

Biomedical Materials, Journal Year: 2024, Volume and Issue: 19(4), P. 042003 - 042003

Published: May 13, 2024

Abstract Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, immunoregulatory activity, play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain functions inner but also inherit characteristics macrophages, making them excellent tools for improving drug delivery therapeutic implications infectious (IDs). In this review, we describe their advantages challenges ID therapy. We first summarize pathological features IDs, providing insight into how to fight them. Next, focus on classification, characteristics, preparation nanoparticles. Finally, comprehensively progress combating including delivery, inhibition killing pathogens, modulation. At end look forward aspect is presented.

Language: Английский

Citations

5
A helical LC3-interacting region mediates the interaction between the retroviral restriction factor Trim5α and mammalian autophagy-related ATG8 proteins DOI Creative Commons
J.R. Keown,

Moyra M. Black,

Aaron Ferron

et al.

Journal of Biological Chemistry, Journal Year: 2018, Volume and Issue: 293(47), P. 18378 - 18386

Published: Oct. 3, 2018

The retroviral restriction factor tripartite motif–containing 5α (Trim5α) acts during the early postentry stages of life cycle to block infection by a broad range retroviruses, disrupting reverse transcription and integration. mechanism this is poorly understood, but it has recently been suggested involve recruitment components autophagy machinery, including members mammalian autophagy-related 8 (ATG8) family involved in targeting proteins autophagosome. To better understand molecular details interaction, here we utilized analytical ultracentrifugation characterize binding six ATG8 isoforms determined crystal structure Trim5α Bbox coiled-coil region complex with one member proteins, protein LC3 B (LC3B). We found that binds all ATG8s that, unlike typical LC3-interacting (LIR) through β-strand motif comprising approximately residues, LC3B via α-helical region. orientation demonstrated could be accommodated within assembly can bind capsid. However, mutation interface does not affect restriction. Comparison linear LIR our atypical helical reveals conservation presentation residues are required for interaction LC3B. This observation expands LC3B-binding include motifs demonstrates link between

Language: Английский

Citations

45