Single-Cell Analysis Reveals Heterogeneity of Virus Infection, Pathogenicity, and Host Responses: HIV as a Pioneering Example

Annual Review of Virology, Journal Year: 2020, Volume and Issue: 7(1), P. 333 - 350

Published: Sept. 29, 2020

While analyses of cell populations provide averaged information about viral infections, single-cell offer individual consideration, thereby revealing a broad spectrum diversity as well identifying extreme phenotypes that can be exploited to further understand the complex virus-host interplay. Single-cell technologies applied in context human immunodeficiency virus (HIV) infection proved valuable tools help uncover specific biomarkers novel candidate players interactions. This review aims at providing an updated overview field HIV and acquired knowledge on infection, latency, host response. Although is pioneering example, similar approaches have proven for elucidating behavior interplay range other viruses.

Language: Английский

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A Role of Intracellular Toll-Like Receptors (3, 7, and 9) in Response to Mycobacterium tuberculosis and Co-Infection with HIV

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6148 - 6148

Published: Aug. 26, 2020

Mycobacterium tuberculosis (Mtb) is a highly infectious acid-fast bacillus and known to cause (TB) in humans. It leading of death from sole agent, with an estimated 1.5 million deaths yearly worldwide, up one third the world’s population has been infected TB. The virulence susceptibility Mtb are further amplified presence Human Immunodeficiency Virus (HIV). Coinfection HIV forms lethal combination. Previous studies had demonstrated synergistic effects HIV, disease accelerating progression other through multiple mechanisms, including modulation immune response these two pathogens. endosomal pattern recognition receptors pathogens, specifically toll-like (TLR)-3, -7, -9, not elucidated, some producing mixed results. This article seeks review roles TLR-3, -9 infection, as well Mtb-HIV-coinfection via Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing INF-β (TRIF)-dependent myeloid differentiation factor 88 (MyD88)-dependent pathways.

Language: Английский

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The CD8⁺T Cell Noncytotoxic Antiviral Responses

Microbiology and Molecular Biology Reviews, Journal Year: 2021, Volume and Issue: 85(2)

Published: May 11, 2021

The CD8

Language: Английский

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Toll-Like Receptor (TLR) Signaling Enables Cyclic GMP-AMP Synthase (cGAS) Sensing of HIV-1 Infection in Macrophages

mBio, Journal Year: 2021, Volume and Issue: 12(6)

Published: Nov. 30, 2021

HIV-1 replicates in cells that express a wide array of innate immune sensors and may do so simultaneously with other pathogens. How coexisting stimulus influences the outcome sensing, however, remains poorly understood. Here, we demonstrate activation second signaling pathway enables cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) response to infection. We used RNA sequencing determine alone induced few or no signs an IFN-I THP-1 cells. In contrast, when supplemented suboptimal levels bacterial lipopolysaccharide (LPS), infection triggered production elevated significant upregulation interferon-stimulated genes. LPS-mediated enhancement upon infection, which was observed primary macrophages, lost by blocking reverse transcription hyperstable capsid, pointing viral DNA being essential immunostimulatory molecule. LPS also synergistically enhanced (cGAMP), messenger cGAS. These observations suggest sensor cGAS is responsible for IFN concert receptor Toll-like 4 (TLR4). Small amounts TLR2 agonist cooperate induce production. results how subtle immunomodulatory activity renders capable eliciting through positive cross talk between TLR sensing pathways. IMPORTANCE Innate hallmark pathogenesis. Thus, it critical understand elicits responses. this work, show macrophages leads robust (IFN) only event initiated Our not sufficient triggering strong response. find membrane components, are recognized endosomal sensors, enable IFNs genes This dependent on synthesis prevented stable role provide new insights into different recognition pathways synergize during

Language: Английский

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

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

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