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Viruses 2016, 8(7), 189; doi:10.3390/v8070189

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

1
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
2
Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 29 February 2016 / Revised: 8 June 2016 / Accepted: 14 June 2016 / Published: 7 July 2016
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [2792 KB, uploaded 7 July 2016]   |  

Abstract

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. View Full-Text
Keywords: SIVcpz; HIV; Nef; truncated Nef peptide SIVcpz; HIV; Nef; truncated Nef peptide
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sabino Cunha, M.; Lima Sampaio, T.; Peterlin, B.M.; Jesus da Costa, L. A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny. Viruses 2016, 8, 189.

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