The ISG15-Protease USP18 Is a Pleiotropic Enhancer of HIV-1 Replication

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 485 - 485

Published: March 22, 2024

The innate immune response to viruses is formed in part by interferon (IFN)-induced restriction factors, including ISG15, p21, and SAMHD1. IFN production can be blocked the ISG15-specific protease USP18. HIV-1 has evolved circumvent host surveillance. This mechanism might involve In our recent studies, we demonstrate that infection induces USP18, which dramatically enhances replication abrogating antiviral function of p21. USP18 downregulates p21 accumulating misfolded dominant negative p53, inactivates wild-type p53 transactivation, leading upregulation key enzymes involved de novo dNTP biosynthesis pathways inactivated Despite USP18-mediated increase DNA infected cells, it intriguing note cGAS-STING-mediated sensing viral abrogated. Indeed, expression or knockout ISG15 inhibits HIV-1. We STING ISGylated at residues K224, K236, K289, K347, K338, K370. inhibition K289-linked ISGylation suppresses its oligomerization induction. propose human a novel factor potentially contributes multiple ways replication.

Language: Английский

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Targeting uracil-DNA glycosylases for therapeutic outcomes using insights from virus evolution

Future Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 11(11), P. 1323 - 1344

Published: June 1, 2019

Ung-type uracil-DNA glycosylases are frontline defenders of DNA sequence fidelity in bacteria, plants and animals; Ungs also directly assist both innate humoral immunity. Critically important viral pathogenesis, whether acting for or against persistence, have therapeutic relevance to cancer, microbial parasitic diseases. Ung catalytic specificity is uniquely conserved, yet selective antiviral drugging the pocket tractable. However, more promising precision therapy approaches present themselves via insights from strategies, including sequestration adaptation noncanonical roles. A universal inhibition mechanism, converged upon by unrelated viruses, could inform design compounds inhibit specific distinct Ungs. Extrapolating current developments, character such novel chemical entities proposed.

Language: Английский

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Analysis of Severe Acute Respiratory Syndrome 2 Replication in Explant Cultures of the Human Upper Respiratory Tract Reveals Broad Tissue Tropism of Wild-Type and B.1.1.7 Variant Viruses

The Journal of Infectious Diseases, Journal Year: 2021, Volume and Issue: 224(12), P. 2020 - 2024

Published: Oct. 13, 2021

Abstract Background The upper respiratory tract (URT) is the primary entry site for severe acute syndrome 2 (SARS-CoV-2) and other viruses, but its involvement in viral amplification pathogenesis remains incompletely understood. Methods In this study, we investigated nasal epithelial cultures, as well vital explanted tissues, to scrutinize tropism of wild-type SARS-CoV-2 recently emerged B.1.1.7 variant. Results Our analyses revealed a widespread replication competence polarized epithelium examined URT salivary gland which was also shared by virus. Conclusions our analyses, highlighted active role these anatomic sites coronavirus disease 2019.

Language: Английский

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Attenuation of Equine Lentivirus Alters Mitochondrial Protein Expression Profile from Inflammation to Apoptosis

Journal of Virology, Journal Year: 2019, Volume and Issue: 93(21)

Published: Aug. 8, 2019

Equine infectious anemia virus (EIAV) is an equine lentivirus similar to HIV-1, targets host immune cells, and causes a life-long infection in horses. The Chinese live EIAV vaccine attenuated from long-term passaging of highly virulent strain vitro parent pathogenic (EIAVDLV34) induces inflammatory storm cause severe pathological injury animals. However, the (EIAVDLV121) high level apoptosis eliminate infected cells. To investigate how these processes are regulated, we performed comparative proteomics analysis functional study monocyte-derived macrophages (eMDMs) found that divergent mitochondrial protein expression profiles caused by strains with different virulence led disparate function, morphology, metabolism. This turn promoted distinct transformation macrophage polarization intrinsic apoptosis. In EIAVDLV34-infected glycolysis increased fragmentation were induced, resulting M1-polarized proinflammatory-type subsequent production strong response. Following EIAVDLV121, cells transformed into M2-polarized anti-inflammatory inhibition glycolysis. this case, decrease membrane potential impairment electron transport chain levels reactive oxygen species. These results correlated viral pathogenicity loss may help provide understanding key mechanism lentiviral attenuation.IMPORTANCE infection, working pattern function cell can be through impact on mitochondria. It still unknown response changes viruses process attenuation. EIAVDLV121 only effective for large-scale use world. EIAVDLV34 strain. Unlike EIAVDLV34-induced inflammation storms, induce For first time, that, after profile altered, M1-polarized-type pathway activated EIAVDLV121-infected studies shed light between drive cellular responses, especially

Language: Английский

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Viral Emerging Pathogen Evolution

Elsevier eBooks, Journal Year: 2019, Volume and Issue: unknown, P. 35 - 51

Published: Sept. 20, 2019

Language: Английский

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