Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells DOI Creative Commons

Sallieu Jalloh,

I A Hughes,

Hisashi Akiyama

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Despite the success of antiretroviral therapy (ART) in suppressing plasma viremia people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology comorbidities. Infection long-lived innate immune cells, such as tissue-resident macrophages microglia may production chronic inflammation. We recently reported that de-novo cytoplasmic HIV-1 intron-containing (icRNA) leads MDA5 MAVS-dependent sensing induction type I IFN responses, demonstrating HIV icRNA a pathogen-associated molecular pattern (PAMP). In this report, we show also induces NLRP1 inflammasome activation IL-1β secretion RLR- endosomal TLR-independent manner. both either replication-competent or single-cycle induced secretion, which was attenuated when prevented. While blocked by treatment caspase-1 inhibitors knockdown HIV- infected macrophages, overexpression significantly enhanced an HIV-icRNA-dependent Immunoprecipitation analysis revealed interaction icRNA, but not multiply-spliced RNA, NLRP1, suggesting sufficient trigger activation. Together, these findings reveal pathway de novo expressed myeloid cells.

Language: Английский

SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages DOI Creative Commons
Giovanny J. Martínez-Colón, Kalani Ratnasiri, Richard Chen

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(674)

Published: Sept. 22, 2022

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet underlying mechanism unknown. To explore whether severe acute respiratory syndrome 2 (SARS-CoV-2) infection tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled response SARS-CoV-2 in vitro. In cases, identified RNA adipocytes an inflammatory infiltrate. We two distinct cellular targets infection: a subset tissue-resident macrophages. Mature were permissive infection; although macrophages abortively infected, initiated responses within both infected bystander preadipocytes. These data suggest that could contribute severity through replication virus induction local systemic driven

Language: Английский

Citations

87
ACE2-dependent and -independent SARS-CoV-2 entries dictate viral replication and inflammatory response during infection DOI
Tianhao Duan, Changsheng Xing, Junjun Chu

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(4), P. 628 - 644

Published: March 21, 2024

Language: Английский

Citations

21
Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release DOI Open Access
Larisa I. Labzin,

Keng Yih Chew,

Kathrin Eschke

et al.

Science Signaling, Journal Year: 2023, Volume and Issue: 16(782)

Published: April 25, 2023

Macrophages are key cellular contributors to the pathogenesis of COVID-19, disease caused by virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset macrophages at sites infection in humans. Here, we investigated whether can enter macrophages, replicate, and release new viral progeny; need sense replicating drive cytokine release; and, if so, involved these mechanisms. We found that could enter, but did not replicate within, ACE2-deficient human primary induce proinflammatory expression. By contrast, overexpression THP-1–derived permitted entry, processing replication, virion release. ACE2-overexpressing THP-1 sensed active replication triggered proinflammatory, antiviral programs mediated kinase TBK-1 limited prolonged These findings help elucidate role its absence macrophage responses infection.

Language: Английский

Citations

33
Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation DOI Creative Commons
Obdulio García-Nicolás,

Aurélie Godel,

Gert Zimmer

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(7), P. 835 - 849

Published: May 30, 2023

Abstract Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) resistant unresponsive to SARS-CoV-2 infection. Here, we demonstrate upon phagocytosis of SARS-CoV-2-infected cells, MDMs activated secrete IL-6 TNF. Importantly, in turn mediate activation plasmacytoid dendritic cells (pDCs), leading the secretion high levels IFN-α Furthermore, pDC promoted production by MDMs. This kind was dependent on direct integrin-mediated cell‒cell contacts involved stimulation TLR7 STING signaling pathways. Overall, present study describes a novel potent pathway is linked macrophage-mediated clearance infected cells. These findings suggest infection rate may lead exaggerated responses, which contribute tissue damage disease.

Language: Английский

Citations

24
The viral oncogenesis of COVID-19 and its impact on cancer progression, long-term risks, treatment complexities, and research strategies DOI Creative Commons
Moawiah M. Naffaa, Ola A Al-Ewaidat

Exploration of Medicine, Journal Year: 2025, Volume and Issue: 6

Published: April 28, 2025

The interaction between cancer and coronavirus disease 2019 (COVID-19) poses significant challenges, particularly for immunocompromised individuals who are at heightened risk acute infections long-term complications. pandemic has exacerbated existing vulnerabilities in care by disrupting treatment protocols delaying diagnoses, leading to worsened health outcomes. This article emphasizes the importance of investigating potential impact severe respiratory syndrome 2 (SARS-CoV-2) on progression highlights need effective strategies protect this high-risk population. Long-term consequences, including emergence long COVID, further emphasize ongoing surveillance comprehensive healthcare planning patients during after pandemics. A multifaceted approach is essential, incorporating vaccination, timely therapeutic interventions, sustained support with lingering symptoms. also discusses urges continued research into oncogenic risks associated SARS-CoV-2, which crucial enhancing our understanding broader implications COVID-19 informing public aimed safeguarding future Moreover, data collection development refined clinical guidelines vital improving patient outcomes preparing systems crises. Additionally, mechanisms SARS-CoV-2 may increase susceptibility, chronic inflammation, cellular senescence, immune dysregulation. Understanding these elucidating virus’s potential, among survivors infections. Ensuring continuity resilience global crises requires mitigate disruptions, enhance access screenings treatments, address specific challenges faced experiencing COVID.

Language: Английский

Citations

0
Effects of diarylbutane lignans from Schisandra chinensis fruit on SARS-CoV-2 3CLpro and PLpro and their in vitro anti-inflammatory properties DOI Creative Commons
Bin Li, Liansheng Qiao, Qi Xiao

et al.

Phytomedicine Plus, Journal Year: 2023, Volume and Issue: 3(2), P. 100432 - 100432

Published: March 11, 2023

Schisandra chinensis fruit is a well-known traditional Chinese medicine (TCM), whose extract has potent inhibitory effect on the severe acute respiratory syndrome-coronavirus-2 (SARS‑CoV‑2) 3-chymotrypsin-like protease (3CLpro) and papain-like (PLpro).This work aims to find active components from of S. against SARS‑CoV‑2 3CLpro PLpro.The chemical constituents were retrieved based electronic databases, such as Web Science, PubMed, Medline Plus, CNKI. Molecular docking was used screen PLpro. Potential hit compounds further evaluated by enzymatic activity assay. Furthermore, anti-inflammatory activities explored using phorbol-12-myristate-13-acetate (PMA)-induced THP1 cells model.In this work, we 75 fruit, including 62 dibenzocyclooctadiene-type lignans, 3 diarylbutane-type 2 tetrahydrofuran-type 8 nortriterpenoids. Combining molecular study in vitro experiments, found that pregomisin (63), meso‑dihydroguaiaretic acid (64), nordihydroguaiaretic (65) could potently inhibit with IC50 values 3.07 ± 0.38, 4.12 6.06 0.62 μM, respectively, PLpro 5.23 0.33, 4.24 0.46, 16.28 0.54 respectively. Interestingly, 63, 64, 65 also have regulating inflammatory response vitro.Our results suggest may be promising SARS-CoV-2 inhibitors anti-inflammatory.

Language: Английский

Citations

10
SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner DOI Creative Commons

Moe Kobayashi,

Nobuyuki Kobayashi,

Koichiro Deguchi

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 27, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving mutations in the Spike protein to evade humoral immunity. Respiratory tract antiviral IgA antibodies are superior circulating IgG preventing SARS-CoV-2 infection. However, role of innate immune signals required for induction mucosal against infection unknown. Here we show that hamsters recovered from ancestral cross-protected heterologous alpha, gamma, delta, and omicron BA.1 variants. Intranasal vaccination with an inactivated whole virus vaccine completely protects In addition, intranasal boost mice unadjuvanted induces robust levels anti-Spike a Furthermore, our findings suggest MyD88 MAVS play memory response following booster These provide useful basis development cross-protective vaccines

Language: Английский

Citations

0
A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a DOI
Zi‐Wei Ye, Chon Phin Ong,

Hehe Cao

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 114, P. 105662 - 105662

Published: March 25, 2025

Language: Английский

Citations

0
Role of Siglecs in viral infections: A double-edged sword interaction DOI Creative Commons
Dàlia Raϊch‐Regué, Patricia Resa‐Infante, Marçal Gallemí

et al.

Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 90, P. 101113 - 101113

Published: Aug. 16, 2022

Sialic-acid-binding immunoglobulin-like lectins are cell surface immune receptors known as Siglecs that play a paramount role modulators of immunity. In recent years, research has underscored how the underlaying biology this family influences outcome viral infections. While needed to promote effective antiviral responses, they can also pave way dissemination within tissues. Here, we review preclinical findings focusing on interplay between and viruses may translate into promising broad-spectrum therapeutic interventions or key biomarkers monitor course

Language: Английский

Citations

16
Overreactive macrophages in SARS-CoV-2 infection: The effects of ACEI DOI Creative Commons
Dominik Felkle, Katarzyna Zięba,

Konrad Kaleta

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110858 - 110858

Published: Sept. 12, 2023

Among various factors influencing the course of SARS-CoV-2 infection in humans, macrophage overactivation is considered main cause cytokine storm that leads to severe complications COVID-19. Moreover, increased expression angiotensin converting enzyme 2 (ACE2), an obligatory entry receptor coronavirus, caused by treatment with ACE inhibitors (ACEI) lowered overall confidence safety these drugs. However, analysis coronavirus patients treated ACEI does not support concerns. Instead, beneficial effect on macrophages has increasingly been emphasized. This includes their anti-inflammatory activation and consequent reduction risk disease life-threatening complications. Herein, we summarize current knowledge understanding dual role infection, a special focus postulated mechanisms underlying effects targeting ACEI. These seem involve stimulation II type Mas receptors 1-7, intensively produced due up-regulation ACE2 macrophages, as well direct inhibition hyper-responsiveness The impact may also lead effective antiviral response ACE2.

Language: Английский

Citations

9