Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

Huarte, Nerea; Lorizate, Maier; Pérez‐Payá, Enrique; Nieva, José L.

doi:10.2174/156802611798808460

Cited by 5 publications

(3 citation statements)

References 118 publications

(116 reference statements)

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“…Thus, they used leakage of aqueous contents induced by the synthetic HIV-FP as a surrogate assay for self-oligomerization in membranes. Subsequently, a D-hexapeptide library was screened for its capacity to block FP-induced leakage (for a description of this assay see also (Huarte et al, 2011)). Using this approach two hexapeptides were identified that blocked gp41-induced fusion, thereby supporting the FP region as a potential target for inhibitor development.…”

Section: Prospects As Therapeutic Targetsmentioning

confidence: 99%

“…Thus, the themes of glycoprotein structure-function common to all enveloped viruses are highly significant for the understanding of the general mechanism of protein-mediated fusion Chernomordik and Kozlov, 2003;Cohen and Melikyan, 2004;Harrison, 2008;Hernandez et al, 1996;Kozlov et al, 2010;Lentz et al, 2000;Melikyan, 2008). In addition, the conserved elements of these machineries, transiently or permanently exposed on the virion surface, provide clinical targets for development of inhibitors (antivirals) and immunogens (vaccines) (Blumenthal and Dimitrov, 2007;Doms and Moore, 2000;Eckert and Kim, 2001;Forssmann et al, 2010;Huarte et al, 2011;Munch et al, 2007). Fig.…”

Section: Introduction: Viral Glycoprotein-induced Membrane Fusionmentioning

confidence: 99%

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The three lives of viral fusion peptides

Apellániz

Huarte

Largo

et al. 2014

Chemistry and Physics of Lipids

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Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention.

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Section: Prospects As Therapeutic Targetsmentioning

confidence: 99%

Section: Introduction: Viral Glycoprotein-induced Membrane Fusionmentioning

confidence: 99%

The three lives of viral fusion peptides

Apellániz

Huarte

Largo

et al. 2014

Chemistry and Physics of Lipids

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“…To investigate factors influencing the P16‐mediated enhancement of viral infection, we analyzed the sequence characteristics of the MPER domain. MPER, a highly conserved and Trp‐rich domain in the gp41 transmembrane envelope subunit of HIV‐1, plays an important role in viral fusion and infectivity and thus is targeted by broadly neutralizing antibodies 4E10, 2F5. and Z13e1 .…”

Section: Introductionmentioning

confidence: 99%

A novel modified peptide derived from membrane‐proximal external region of human immunodeficiency virus type 1 envelope significantly enhances retrovirus infection

Zhang

Jiang

Zhang

et al. 2013

Journal of Peptide Science

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Efficient gene transfer is a critical goal in retroviral transduction. Several peptides capable of forming amyloid fibrils, such as the 39-residue semen-derived infection-enhancing peptide (SEVI), have demonstrated the ability to boost retroviral gene delivery. Here, a 13-residue peptide P13 (Ac-(671) NWFDITNWLWYIK(683)) derived from the membrane-proximal external region of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane protein, together with its 16-residue peptide derivative (P16) were found to enhance HIV-1 infection significantly. Both peptides, P13 and P16, could form amyloid fibril structures to potently enhance HIV-1 infectivity. Further investigations showed that both aromatic Trp residues and cationic Lys residues contributed to the enhancement of HIV-1 infection by these two active peptides. P16 could more effectively augment HIV-1 YU-2 infection than SEVI, implying its potential applications as a tool in the lab to improve gene transfer rates.

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Novel neutralising antibodies targeting the N-terminal helical region of the transmembrane envelope protein p15E of the porcine endogenous retrovirus (PERV)

Waechter

Denner

2013

Immunol Res

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Previously, immunising different species with the transmembrane envelope protein p15E of the porcine endogenous retrovirus (PERV), neutralising antibodies were induced which recognised epitopes in the fusion peptide proximal region (FPPR) and in the membrane-proximal external region (MPER). Only the MPER-specific antibodies were shown to neutralise and these antibodies targeted epitopes in the MPER similarly localised as the epitopes recognised by antibodies broadly neutralising HIV-1 such as 2F5 and 4E10. To study whether neutralising antibodies could be induced immunising with subunits of p15E, recombinant proteins corresponding to the N-terminal, the C-terminal helical region (NHR, CHR) and a p15E with a mutation in the Cys-Cys loop were produced. Whereas none of these antigens induced MPER-specific neutralising antibodies, the animals immunised with the FPPR/NHR subunit and the mutated p15E produced neutralising antibodies binding to the NHR. Therefore, for the first time, antibodies specific for the NHR and neutralising PERV were described.

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Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

Cited by 5 publications

References 118 publications

The three lives of viral fusion peptides

The three lives of viral fusion peptides

A novel modified peptide derived from membrane‐proximal external region of human immunodeficiency virus type 1 envelope significantly enhances retrovirus infection

Novel neutralising antibodies targeting the N-terminal helical region of the transmembrane envelope protein p15E of the porcine endogenous retrovirus (PERV)

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