دورية أكاديمية
أعرض في EDS

A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny.

التفاصيل البيبلوغرافية
العنوان: A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny.
المؤلفون: Sabino Cunha M; Departamento de Virologia-Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373-CCS-Bloco I, Rio de Janeiro 21941-902, Brazil. marcela.scw@gmail.com., Lima Sampaio T; Departamento de Virologia-Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373-CCS-Bloco I, Rio de Janeiro 21941-902, Brazil. ljcosta@micro.ufrj.br., Peterlin BM; Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143, USA. Matija.Peterlin@ucsf.edu., Jesus da Costa L; Departamento de Virologia-Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373-CCS-Bloco I, Rio de Janeiro 21941-902, Brazil. ljcosta@micro.ufrj.br.
المصدر: Viruses [Viruses] 2016 Jul 07; Vol. 8 (7). Date of Electronic Publication: 2016 Jul 07.
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: Virus Replication*, Gene Products, nef/*metabolism , HIV-1/*physiology , Simian Immunodeficiency Virus/*physiology, Animals ; Cell Line ; Frameshift Mutation ; Gene Knockout Techniques ; Gene Products, gag/metabolism ; Gene Products, nef/genetics ; Gene Products, pol/metabolism ; Humans ; Pan troglodytes ; Protein Binding ; Simian Immunodeficiency Virus/genetics
مستخلص: Nef proteins from all primate Lentiviruses, including the simian immunodeficiency virus of chimpanzees (SIVcpz), increase viral progeny infectivity. However, the function of Nef involved with the increase in viral infectivity is still not completely understood. Nonetheless, until now, studies investigating the functions of Nef from SIVcpz have been conducted in the context of the HIV-1 proviruses. In an attempt to investigate the role played by Nef during the replication cycle of an SIVcpz, a Nef-defective derivative was obtained from the SIVcpzWTGab2 clone by introducing a frame shift mutation at a unique restriction site within the nef sequence. This nef-deleted clone expresses an N-terminal 74-amino acid truncated peptide of Nef and was named SIVcpz-tNef. We found that the SIVcpz-tNef does not behave as a classic nef-deleted HIV-1 or simian immunodeficiency virus of macaques SIVmac. Markedly, SIVcpz-tNef progeny from both Hek-293T and Molt producer cells were completely non-infectious. Moreover, the loss in infectivity of SIVcpz-tNef correlated with the inhibition of Gag and GagPol processing. A marked accumulation of Gag and very low levels of reverse transcriptase were detected in viral lysates. Furthermore, these observations were reproduced once the tNef peptide was expressed in trans both in SIVcpzΔNef and HIV-1WT expressing cells, demonstrating that the truncated peptide is a dominant negative for viral processing and infectivity for both SIVcpz and HIV-1. We demonstrated that the truncated Nef peptide binds to GagPol outside the protease region and by doing so probably blocks processing of both GagPol and Gag precursors at a very early stage. This study demonstrates for the first time that naturally-occurring Nef peptides can potently block lentiviral processing and infectivity.
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معلومات مُعتمدة: P50 GM082250 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: HIV; Nef; SIVcpz; truncated Nef peptide
المشرفين على المادة: 0 (Gene Products, gag)
0 (Gene Products, nef)
0 (Gene Products, pol)
تواريخ الأحداث: Date Created: 20160712 Date Completed: 20170926 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4974524
DOI: 10.3390/v8070189
PMID: 27399760
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v8070189