دورية أكاديمية
أعرض في EDS

Different Mutation Tolerance of Lentiviral (HIV-1) and Deltaretroviral (BLV and HTLV) Protease Precursors.

التفاصيل البيبلوغرافية
العنوان: Different Mutation Tolerance of Lentiviral (HIV-1) and Deltaretroviral (BLV and HTLV) Protease Precursors.
المؤلفون: Mótyán JA; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Kassay N; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary., Matúz K; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Tőzsér J; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
المصدر: Viruses [Viruses] 2022 Aug 26; Vol. 14 (9). Date of Electronic Publication: 2022 Aug 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
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 Infections* , HIV Seropositivity* , HIV-1*/genetics , Leukemia Virus, Bovine*/genetics, Deltaretrovirus/genetics ; Endopeptidases/genetics ; HIV Protease/genetics ; Humans ; Mutation ; Peptide Hydrolases/genetics ; Polyproteins/genetics ; Protease Inhibitors/pharmacology
مستخلص: The bovine leukemia virus (BLV) and the human T-lymphothropic viruses (HTLVs) are members of the deltaretrovirus genus of Retroviridae family. An essential event of the retroviral life cycle is the processing of the polyproteins by the viral protease (PR); consequently, these enzymes became important therapeutic targets of the anti-retroviral drugs. As compared to human immunodeficiency viruses (HIVs), the deltaretroviruses have a different replication strategy, as they replicate predominantly in the DNA form, by forcing the infected cell to divide, unlike HIV-1, which replicates mainly by producing a vast number of progeny virions and by reinfection. Due to bypassing the error-prone reverse transcription step of replication, the PRs of deltaretroviruses did not undergo such extensive evolution as HIV PRs and remained more highly conserved. In this work, we studied the abilities of wild-type and modified BLV, HTLV (type 1, 2 and 3), and HIV-1 PRs (fused to an N-terminal MBP tag) for self-processing. We designed a cleavage site mutant MBP-fused BLV PR precursor as well, this recombinant enzyme was unable for self-proteolysis, the MBP fusion tag decreased its catalytic efficiency but showed an unusually low K i for the IB-268 protease inhibitor. Our results show that the HTLV and BLV deltaretrovirus PRs exhibit lower mutation tolerance as compared to HIV-1 PR, and are less likely to retain their activity upon point mutations at various positions, indicating a higher flexibility of HIV-1 PR in tolerating mutations under selective pressure.
Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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فهرسة مساهمة: Keywords: BLV; HIV-1; HTLV; autoproteolysis; bovine leukemia virus; human T-lymphotropic virus; human immunodeficiency virus; protease; retroviral protease; retrovirus
المشرفين على المادة: 0 (Polyproteins)
0 (Protease Inhibitors)
EC 3.4.- (Endopeptidases)
EC 3.4.- (Peptide Hydrolases)
EC 3.4.23.- (HIV Protease)
تواريخ الأحداث: Date Created: 20220923 Date Completed: 20220926 Latest Revision: 20221005
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9505669
DOI: 10.3390/v14091888
PMID: 36146695
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v14091888