Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells DOI Creative Commons

Flavien Brouiller,

Francesca Nadalin, Pierre‐Emmanuel Bonté

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(2), P. 106019 - 106019

Published: Jan. 20, 2023

Sensing of incoming viruses is a pivotal task dendritic cells (DCs). Human primary blood DCs encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification the Axl+DC subset, endowed with unique capacities bind, replicate, transmit HIV-1 prompted us evaluate its anti-viral response. We demonstrate induced two main broad intense transcriptional programs different Axl+DCs potentially by sensors; an NF-κB-mediated program led DC maturation efficient CD4+ T cell activation, mediated STAT1/2 activated type I IFN ISG responses. These responses were absent from cDC2 exposed except when viral replication was allowed. Finally, actively replicating identified quantification transcripts exhibited mixed NF-κB/ISG innate Our results suggest route entry may dictate sensing pathways DCs.

Language: Английский

COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile DOI Creative Commons
Sadanand Fulzele, Bikash Sahay,

Ibrahim Yusufu

et al.

Aging and Disease, Journal Year: 2020, Volume and Issue: 11(3), P. 509 - 509

Published: Jan. 1, 2020

The World health organization (WHO) declared Coronavirus disease 2019 (COVID-19) a global pandemic and severe public crisis. Drastic measures to combat COVID-19 are warranted due its contagiousness higher mortality rates, specifically in the aged patient population. At current stage, lack of effective treatment strategies for innovative approaches need be considered. It is well known that host cellular miRNAs can directly target both viral 3'UTR coding region genome induce antiviral effect. In this study, we did in silico analysis human targeting SARS (4 isolates) (29 recent isolates from different regions) correlated our findings with aging underlying conditions. We found 848 common 873 microRNAs genome. Out total SARS, only 558 commonly present all isolates. Interestingly, 315 unique 290 SARS. also noted out 29 isolates, 19 have identical miRNA targets. Netherland (EPI_ISL_422601), Australia (EPI_ISL_413214), Wuhan (EPI_ISL_403931) showed six, four, four targets, respectively. Furthermore, GO, KEGG pathway involved various age-related signaling diseases. Recent studies suggested some decreased GO identified impaired may low abundance which might one contributing factors increasing severity individuals other Further, vitro vivo needed validate these targets identify potential therapeutic

Language: Английский

Citations

123
The reservoir of latent HIV DOI Creative Commons
Jing Chen, Tong Zhou, Yuan Zhang

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: July 28, 2022

The persistence of latent reservoir the human immunodeficiency virus (HIV) is currently major challenge in curing HIV infection. After infects body, unable to be recognized by body’s immune system. Currently, widely adopted antiretroviral therapy (ART) also unble eliminate it, thus hindering progress treatment. This review discusses existence vault for treatment, its formation and factors affecting formation, cell, tissue localization, methods detection removing reservoir, provide a comprehensive understanding vault, order assist future research play potential role achieving

Language: Английский

Citations

61
Revisiting Regulated Cell Death Responses in Viral Infections DOI Open Access
Rex Devasahayam Arokia Balaya, Thottethodi Subrahmanya Keshava Prasad, Richard K. Kandasamy

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7023 - 7023

Published: June 24, 2022

The fate of a viral infection in the host begins with various types cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, pyroptosis are three major regulated cell death mechanisms that play critical roles response. Cell shrinkage, nuclear condensation, bleb formation, retained membrane integrity all signs osmotic imbalance-driven cytoplasmic swelling early damage necroptosis pyroptosis. Caspase-driven apoptotic demise is considered many circumstances an anti-inflammatory, some pathogens hijack signaling routes to initiate targeted attack against host. In this review, selected by which viruses interfere were discussed in-depth illustrated compiling general principles virus–host-specific molecule interactions.

Language: Английский

Citations

39
Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors DOI Creative Commons
Ashley F. George, Jason Neidleman, Xiaoyu Luo

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115202 - 115202

Published: Jan. 1, 2025

We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 sensors factors (VISORs) simultaneously in single cells, applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped SAMHD1 capsid DNA while CD4

Language: Английский

Citations

1
Regulation of STING activity in DNA sensing by ISG15 modification DOI Creative Commons
Chaohui Lin, Edmund Osei Kuffour, Nina V. Fuchs

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113277 - 113277

Published: Oct. 20, 2023

Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation this cascade achieved post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15). ISG15 deficiency inhibits STING-dependent STING agonist-induced antiviral response. Upon external stimuli, undergoes ISGylation at residues K224, K236, K289, K347, K338, K370. Inhibition K289 suppresses STING-mediated Ⅰ induction inhibiting its oligomerization. Of note, removal alleviates gain-of-function phenotype in STING-associated vasculopathy with onset infancy (SAVI). Molecular modeling suggests an important regulator Taken together, our data demonstrate crucial for activation represents regulatory step viruses autoimmune responses.

Language: Английский

Citations

20
IP6‐stabilised HIV capsids evade cGAS/STING‐mediated host immune sensing DOI Creative Commons
Guido Papa, Anna Albecka, Donna L. Mallery

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(5)

Published: March 27, 2023

Abstract HIV‐1 uses inositol hexakisphosphate (IP6) to build a metastable capsid capable of delivering its genome into the host nucleus. Here, we show that viruses are unable package IP6 lack protection and detected by innate immunity, resulting in activation an antiviral state inhibits infection. Disrupting enrichment results defective capsids trigger cytokine chemokine responses during infection both primary macrophages T‐cell lines. Restoring with single mutation rescues ability infect cells without being detected. Using combination mutants CRISPR‐derived knockout cell lines for RNA DNA sensors, immune sensing is dependent upon cGAS–STING axis independent detection. Sensing requires synthesis viral prevented reverse transcriptase inhibitors or active‐site mutation. These demonstrate required can successfully transit avoid sensing.

Language: Английский

Citations

19
The initial interplay between HIV and mucosal innate immunity DOI Creative Commons

Valeria Caputo,

Martina Libera,

Sofia Sisti

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 30, 2023

Human Immunodeficiency Virus (HIV) is still one of the major global health issues, and despite significant efforts that have been put into studying pathogenesis HIV infection, several aspects need to be clarified, including how innate immunity acts in different anatomical compartments. Given nature as a sexually transmitted disease, demands particular attention mucosal immune response. this scenario, we focused our on interplay between response: mucosae act physical barrier, whose integrity can compromised by virus-cell interaction induces In addition, explored role microbiota facilitating or preventing infection highlighted its changes could influence development opportunistic infections. Although recent progress, proper characterization response missing, further studies are needed understand they helpful for formulation an effective vaccine.

Language: Английский

Citations

18
HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products via the cGAS-STING pathway DOI Creative Commons
Jenna E. Eschbach, Maritza Puray‐Chavez, Shawn Mohammed

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: March 26, 2024

ABSTRACT A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms conical core when it rearranges around dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between stability nucleic acids has not established. Herein, we assessed how manipulating lattice through chemical genetic approaches affects recognition HIV-1. We found that destabilization resulted potent reverse transcription products per se does completely block transcription. Surprisingly, due combined effects enhanced defects nuclear entry, two separate mutants form hyperstable cores induced more potently than destabilizing mutations. At low concentrations allowed accumulation products, CA-targeting compounds GS-CA1 lenacapavir measurably impacted cells modestly HIV. Interestingly, activation observed with viruses containing unstable was abolished by doses lenacapavir. Innate both dependent on cGAS-STING DNA-sensing pathway Overall, our findings demonstrate are finely balanced support minimize cGAS-STING-mediated resulting DNA. IMPORTANCE In particles, proteins enzymes encased proteinaceous composed protein. altering this orthogonal impacts induction responses. Specifically, decreasing results but genomic RNA, cGAS-STING-dependent manner. The recently developed inhibitors Unexpectedly, increased levels cytosolic cDNA, also type I interferon-mediated immunity. Our suggest exposure cytosol host cells.

Language: Английский

Citations

8
Interactions of HIV-1 Capsid with Host Factors and Their Implications for Developing Novel Therapeutics DOI Creative Commons
Shentian Zhuang, Bruce E. Torbett

Viruses, Journal Year: 2021, Volume and Issue: 13(3), P. 417 - 417

Published: March 5, 2021

The Human Immunodeficiency Virus type 1 (HIV-1) virion contains a conical shell, termed capsid, encasing the viral RNA genome. After cellular entry of virion, capsid is released and ensures protection delivery HIV-1 genome to host nucleus for integration. relies on many virus-host factor interactions which are regulated spatiotemporally throughout course infection. In this paper, we will review current understanding highly dynamic capsid-host interplay during early stages replication, namely intracellular trafficking after fusion, nuclear import, uncoating, integration into chromatin. Conventional anti-retroviral therapies primarily target enzymes. Insights structure have resulted in first-in-class, long-acting capsid-targeting inhibitor, GS-6207 (Lenacapavir). This inhibitor binds at interface between protein subunits, site known bind factors, interferes with HIV particle assembly, ordered assembly. Our highlight structure, factors that interact high-throughput screening techniques, specifically genomic proteomic approaches, been can be used identify capsid. Better structural mechanistic insights significantly inform pathogenesis development capsid-centric antiretroviral therapeutics.

Language: Английский

Citations

37
Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses DOI Creative Commons
Jiarui Li, Ester Boix

Virulence, Journal Year: 2021, Volume and Issue: 12(1), P. 444 - 469

Published: March 4, 2021

Owing to the recent outbreak of Coronavirus Disease 2019 (COVID-19), it is urgent develop effective and safe drugs treat present pandemic prevent other viral infections that might come in future. Proteins from our own innate immune system can serve as ideal sources novel drug candidates thanks their safety regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try summarize currently available information on human target pathogens, special focus enveloped single-stranded RNA (ssRNA) viruses. Overall, fight viruses by a combined multifaceted strategy, including enzymatic genome, recognition virus unique patterns, modulation, control stress granule formation, induction autophagy/apoptosis pathways. The review also includes detailed description representative ssRNA strategies interact evade recognition. For comparative purposes, provide an exhaustive revision approved or experimental drugs. Finally, sum up current perspectives development achieve successful eradication infections.

Language: Английский

Citations

36