دورية أكاديمية
أعرض في EDS

Beyond Inhibition: A Novel Strategy of Targeting HIV-1 Protease to Eliminate Viral Reservoirs.

التفاصيل البيبلوغرافية
العنوان: Beyond Inhibition: A Novel Strategy of Targeting HIV-1 Protease to Eliminate Viral Reservoirs.
المؤلفون: Kim JG; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Shan L; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
المصدر: Viruses [Viruses] 2022 May 28; Vol. 14 (6). Date of Electronic Publication: 2022 May 28.
نوع المنشور: Journal Article; Review; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: HIV Protease*/metabolism , HIV-1*/physiology, CARD Signaling Adaptor Proteins/metabolism ; Fusion Proteins, gag-pol/metabolism ; Humans ; Neoplasm Proteins/metabolism ; Reverse Transcriptase Inhibitors/pharmacology
مستخلص: HIV-1 protease (PR) is a viral enzyme that cleaves the Gag and Gag-Pol polyprotein precursors to convert them into their functional forms, a process which is essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. A recent study demonstrated that CARD8 can sense HIV-1 PR activity and induce cell death. While PR typically has low levels of intracellular activity prior to viral budding, premature PR activation can be achieved using certain non-nucleoside reverse transcriptase inhibitors (NNRTIs), resulting in CARD8 cleavage and downstream pyroptosis. Used together with latency reversal agents, the induction of premature PR activation to trigger CARD8-mediated cell killing may help eliminate latent reservoirs in people living with HIV. This represents a novel strategy of utilizing PR as an antiviral target through premature activation rather than inhibition. In this review, we discuss the viral and host substrates of HIV-1 protease and highlight potential applications and advantages of targeting CARD8 sensing of HIV-1 PR.
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معلومات مُعتمدة: R01 AI162203 United States AI NIAID NIH HHS; R21 AI150418 United States AI NIAID NIH HHS; R01AI162203 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: CARD8 inflammasome; HIV/AIDS; latent reservoir; protease; pyroptosis
المشرفين على المادة: 0 (CARD Signaling Adaptor Proteins)
0 (CARD8 protein, human)
0 (Fusion Proteins, gag-pol)
0 (Neoplasm Proteins)
0 (Reverse Transcriptase Inhibitors)
EC 3.4.23.- (HIV Protease)
EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
تواريخ الأحداث: Date Created: 20220624 Date Completed: 20220627 Latest Revision: 20230915
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9231271
DOI: 10.3390/v14061179
PMID: 35746649
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v14061179