HIV-1 Latency in Monocytes/Macrophages DOI Creative Commons
Amit Kumar, Wasim Abbas, Georges Herbein

et al.

Viruses, Journal Year: 2014, Volume and Issue: 6(4), P. 1837 - 1860

Published: April 22, 2014

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and of the monocyte/macrophage lineage. HIV pathogenesis is characterized by depletion lymphocytes presence a population in which latency has been established called HIV-1 reservoir. Highly active antiretroviral therapy (HAART) significantly improved life infected patients. However, complete eradication from individuals not possible without targeting latent sources infection. establishes infection resting findings indicate that can also be Monocyte/macrophage lineage includes among others, monocytes, macrophages brain resident macrophages. These are relatively more resistant to apoptosis induced HIV-1, thus important stable hideouts virus. Much effort made direction eliminating T-cell reservoirs. it impossible achieve cure for considering these neglected reservoirs, In this review we will describe our current understanding mechanism how such specifically eliminated host.

Language: Английский

cGAS in action: Expanding roles in immunity and inflammation DOI Open Access
Andrea Ablasser, Zhijian J. Chen

Science, Journal Year: 2019, Volume and Issue: 363(6431)

Published: March 8, 2019

DNA is highly immunogenic. It represents a key pathogen-associated molecular pattern (PAMP) during infection. Host can, however, also act as danger-associated (DAMP) and elicit strong inflammatory responses. The cGAS-STING pathway has emerged major that detects intracellular DNA. Here, we highlight recent advances on how cGAS STING mediate responses these are regulated, allowing cells to readily respond infections noxious agents while avoiding the inappropriate sensing of self-DNA. A particular focus placed role in context sterile conditions. Manipulating or may open door for new therapeutic strategies treatment acute chronic inflammation relevant many human diseases.

Language: Английский

Citations

822
Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature DOI
Gillian Rice, Paul R. Kasher, Gabriella Forte

et al.

Nature Genetics, Journal Year: 2012, Volume and Issue: 44(11), P. 1243 - 1248

Published: Sept. 23, 2012

Language: Английский

Citations

807
SAMHD1 restricts HIV-1 infection in resting CD4+ T cells DOI

Hanna-Mari Baldauf,

Xiaoyu Pan,

Elina Erikson

et al.

Nature Medicine, Journal Year: 2012, Volume and Issue: 18(11), P. 1682 - 1688

Published: Sept. 12, 2012

Language: Английский

Citations

556
Rules of Engagement: Molecular Insights from Host-Virus Arms Races DOI
Matthew D. Daugherty, Harmit S. Malik

Annual Review of Genetics, Journal Year: 2012, Volume and Issue: 46(1), P. 677 - 700

Published: Nov. 13, 2012

Mammalian genes and genomes have been shaped by ancient ongoing challenges from viruses. These genetic imprints can be identified via evolutionary analyses to reveal fundamental details about when (how old), where (which protein domains), how (what are the functional consequences of adaptive changes) host-virus arms races alter proteins involved. Just as extreme amino acid conservation serve identify key immutable residues in enzymes, positively selected point molecular recognition interfaces between host viral that adapted counter-adapted a long series classical Red Queen conflicts. Common rules for strategies employed both hosts viruses emerged case studies innate immunity primates. We now poised use these transition retrospective view specific predictions which face pathogen antagonism those conflicts transform virus evolution.

Language: Английский

Citations

521
Intrinsic antiviral immunity DOI
Nan Yan, Zhijian J. Chen

Nature Immunology, Journal Year: 2012, Volume and Issue: 13(3), P. 214 - 222

Published: Feb. 16, 2012

Language: Английский

Citations

488
Restricting retrotransposons: a review DOI Creative Commons
John L. Goodier

Mobile DNA, Journal Year: 2016, Volume and Issue: 7(1)

Published: Aug. 11, 2016

Retrotransposons have generated about 40 % of the human genome. This review examines strategies cell has evolved to coexist with these genomic "parasites", focussing on non-long terminal repeat retrotransposons humans and mice. Some restriction factors for retrotransposition, including APOBECs, MOV10, RNASEL, SAMHD1, TREX1, ZAP, also limit replication retroviruses, HIV, are part intrinsic immune system cell. Many proteins act in cytoplasm degrade retroelement RNA or inhibit its translation. nucleus involve DNA repair enzymes epigenetic processes methylation histone modification. RISC piRNA pathway protect germline. Retrotransposon control is relaxed some types, such as neurons brain, stem cells, certain types disease cancer, implications health disease. considers potential pitfalls interpreting retrotransposon-related data, well issues consider future research.

Language: Английский

Citations

400
The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells DOI Creative Commons
Xavier Lahaye, Takeshi Satoh, Matteo Gentili

et al.

Immunity, Journal Year: 2013, Volume and Issue: 39(6), P. 1132 - 1142

Published: Nov. 21, 2013

Language: Английский

Citations

358
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 DOI Creative Commons

Alexandra Cribier,

Benjamin Descours,

Ana Luiza Chaves Valadão

et al.

Cell Reports, Journal Year: 2013, Volume and Issue: 3(4), P. 1036 - 1043

Published: April 1, 2013

SAMHD1 restricts HIV-1 replication in myeloid and quiescent CD4+ T cells. Here, we show that restriction activity is regulated by phosphorylation. interacts with cyclin A2/cdk1 only cycling Cyclin A2/CDK1 phosphorylates at the Threonine 592 residue both vitro vivo. Phosphorylation of Thr592 correlates loss its ability to restrict HIV-1. Indeed, while PMA treatment proliferating THP1 cells results reduced phosphorylation, activation resting peripheral blood mononuclear (PBMCs) purified increased phosphorylation Thr592. Interestingly, found type 1 interferon reinforcing link between antiviral activity. Unlike wild-type SAMHD1, a phosphorylation-defective mutant was able PMA-treated untreated Our uncover as key regulatory mechanism

Language: Английский

Citations

357
Evolutionary conflicts between viruses and restriction factors shape immunity DOI Open Access
Nisha K. Duggal, Michael Emerman

Nature reviews. Immunology, Journal Year: 2012, Volume and Issue: 12(10), P. 687 - 695

Published: Sept. 14, 2012

Language: Английский

Citations

345
Furin‐mediated protein processing in infectious diseases and cancer DOI Creative Commons

Elisabeth Braun,

Daniel Sauter

Clinical & Translational Immunology, Journal Year: 2019, Volume and Issue: 8(8)

Published: Jan. 1, 2019

Proteolytic cleavage regulates numerous processes in health and disease. One key player is the ubiquitously expressed serine protease furin, which cleaves a plethora of proteins at polybasic recognition motifs. Mammalian substrates furin include cytokines, hormones, growth factors receptors. Thus, it not surprising that aberrant activity associated with variety disorders including cancer. Furthermore, enzymatic exploited by viral bacterial pathogens, thereby enhancing their virulence spread. In this review, we describe physiological pathophysiological discuss how dysregulation simple proteolytic event may promote infectious diseases major focus role glycoprotein maturation pathogenicity. We also outline cellular mechanisms regulating expression activation summarise current approaches target for therapeutic intervention.

Language: Английский

Citations

323