Impaired influenza A virus replication by the host restriction factor SAMHD1 which inhibited by PA-mediated dephosphorylation of the host transcription factor IRF3 DOI Creative Commons
Zhilei Zhao, Shuyi Han, Qingxun Zhang

et al.

Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 29, 2024

Abstract Background Influenza A virus (IAV) can cause severe and life-threatening illness in humans animals. Therefore, it is important to search for host antiviral proteins elucidate their mechanisms the development of potential treatments. As a part human innate immunity, restriction factors inhibit replication viruses, among which SAM HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) restrict such as HIV enterovirus EV71. Viruses also developed countermeasures arms race with hosts. There are few reports about whether SAMHD1 has effect on IAV. Methods To investigate impact IAV infection expression A549 cells, we infected cells varying multiplicity (MOI) collected cell samples at different time points WB RT-qPCR analysis detect viral protein levels. The level culture supernatant was determined using TCID50 assay. Luciferase assay used reveal that H5N1 polymerase acidic (PA) affected activity promoter. assess capacity SAMHD1, generated knockdown overexpressed line detecting replication. Results In this study, observed intracellular PA downregulate by affecting transcriptional promoter activity. We found SAMHD1's ability related phosphorylation 592-tyrosine. Conclusions conclusion, may affect IAVs factor be countered PA. Furthermore, target developing drugs.

Language: Английский

New mitochondrial DNA synthesis enables NLRP3 inflammasome activation DOI
Zhenyu Zhong, Shuang Liang, Elsa Sánchez‐López

et al.

Nature, Journal Year: 2018, Volume and Issue: 560(7717), P. 198 - 203

Published: July 24, 2018

Language: Английский

Citations

928
Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1 DOI Creative Commons
Marta Colomer-Lluch,

Alba Ruiz,

Arnaud Moris

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Dec. 6, 2018

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps the cycle, some also act as innate sensors triggering responses against infections. Accumulating evidence suggests an additional role for in promoting antiviral immunity combat viruses. Here, we review recent progress our understanding on how factors, particularly APOBEC3G, SAMHD1, Tetherin, TRIM5α have cell-autonomous potential induce resistance HIV-1 while adaptive immune responses. Also, provide overview these may connect with protein degradation pathways modulate anti-HIV-1 responses, summarize factors-based therapeutics. This brings global perspective influence restrictions intrinsic, innate, opening up novel research avenues therapeutic strategies fields drug discovery, gene therapy, vaccines control

Language: Английский

Citations

152
Monogenic Lupus: A Developing Paradigm of Disease DOI Creative Commons

Jessie M. Alperin,

Lourdes Ortiz‐Fernández, Amr H. Sawalha

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Oct. 30, 2018

Monogenic lupus is a form of systemic erythematosus (SLE) that occurs in patients with single gene defect. This rare variant generally presents early onset severe disease, especially affecting the kidneys and central nervous system. To date, significant number genes have been implicated monogenic lupus, providing valuable insights into very complex disease process. Throughout this review, we will summarize reported to be associated or lupus-like diseases, pathogenic mechanisms affected by mutations involved upon inducing autoimmunity.

Language: Английский

Citations

137
Nucleases Acting at Stalled Forks: How to Reboot the Replication Program with a Few Shortcuts DOI Open Access
Philippe Pasero, Alessandro Vindigni

Annual Review of Genetics, Journal Year: 2017, Volume and Issue: 51(1), P. 477 - 499

Published: Nov. 27, 2017

In a lifetime, human being synthesizes approximately 2×10 16 meters of DNA, distance that corresponds to 130,000 times the between Earth and Sun. This daunting task is executed by thousands replication forks, which progress along chromosomes frequently stall when they encounter DNA lesions, unusual structures, RNA polymerases, or tightly-bound protein complexes. To complete synthesis before onset mitosis, eukaryotic cells have evolved complex mechanisms process restart arrested forks through coordinated action multiple nucleases, topoisomerases, helicases. this review, we discuss recent advances in understanding role regulation nucleases acting at stalled with focus on nucleolytic degradation nascent commonly referred as fork resection. We also effects deregulated resection genomic instability unscheduled activation interferon response under stress conditions.

Language: Английский

Citations

108
Restriction by SAMHD1 Limits cGAS/STING-Dependent Innate and Adaptive Immune Responses to HIV-1 DOI Creative Commons
Jonathan Maelfait, Anne Bridgeman,

Adel Benlahrech

et al.

Cell Reports, Journal Year: 2016, Volume and Issue: 16(6), P. 1492 - 1501

Published: July 29, 2016

SAMHD1 is a restriction factor for HIV-1 infection. mutations cause the autoinflammatory Aicardi-Goutières syndrome that characterized by chronic type I interferon (IFN) secretion. We show spontaneous IFN response in SAMHD1-deficient cells and mice requires cGAS/STING cytosolic DNA-sensing pathway. provide genetic evidence cell-autonomous control of lentivirus infection myeloid limits virus-induced production IFNs induction co-stimulatory markers. This program cell activation required reverse transcription, cGAS STING, signaling through receptor. Furthermore, reduced virus-specific cytotoxic T vivo. Therefore, virus magnitude responses. demonstrates competition between subsequent innate adaptive immune responses, concept with important implications treatment

Language: Английский

Citations

103
SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells DOI Creative Commons
Serena Bonifati, Michele B. Daly,

Corine St. Gelais

et al.

Virology, Journal Year: 2016, Volume and Issue: 495, P. 92 - 100

Published: May 13, 2016

Language: Английский

Citations

89
Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism DOI
Sébastien Levesque,

Andrea Cosentino,

Archana Verma

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

Language: Английский

Citations

10
Juvenile-onset systemic lupus erythematosus (jSLE) – Pathophysiological concepts and treatment options DOI
Christian M. Hedrich, Eve Smith, Michael W. Beresford

et al.

Best Practice & Research Clinical Rheumatology, Journal Year: 2017, Volume and Issue: 31(4), P. 488 - 504

Published: Aug. 1, 2017

Language: Английский

Citations

87
A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? DOI Creative Commons
Sabrina Schreiner, Michael Nassal

Viruses, Journal Year: 2017, Volume and Issue: 9(5), P. 125 - 125

Published: May 22, 2017

Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins episomal minichromosome, cccDNA acts template for new RNAs, ensuring formation progeny virions. Hence, represents the persistence reservoir that not directly targeted by current anti-HBV therapeutics. Eliminating will thus be heart cure chronic B. The low production most experimental models and associated problems reliable quantitation have long hampered deeper understanding molecular biology. Recent advancements including cccDNA-dependent cell culture systems begun identify select host repair enzymes usurps conversion. While this list bound grow, it may represent just one facet broader interaction damage response (DDR), network pathways sense aberrant structures process profoundly affect cycle, up inducing death if fails. Given divergent interactions between other viruses DDR intriguing see how copes multipronged system.

Language: Английский

Citations

84
CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir DOI Creative Commons
Roger Badía, Ester Ballana,

Marc Castellví

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: July 10, 2018

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells an vitro model of quiescent CD4 T cells. Here we show that stimulation CD4+ with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression the activation markers HLA-DR CD69. HIV-1 infection increases expression. 79.2% CD32+/CD4+ from HIV+ individuals under antiretroviral treatment were HLA-DR+. Resting infected generally results higher integration provirus. We observe no difference provirus or replication-competent inducible latent CD32+ CD32- individuals. Our demonstrate expression is a marker cell raises questions regarding immune resting status harboring proviruses.

Language: Английский

Citations

67