The activity of Nef on HIV-1 infectivity

Basmaciogullari, Stéphane; Pizzato, Massimo

doi:10.3389/fmicb.2014.00232

Cited by 75 publications

(60 citation statements)

References 167 publications

(192 reference statements)

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“…5A). This was expected, as Nef affects various steps of viral replication (68,69). Nonetheless, HIV ΔNef -infected cells activated HS clones (F12 and L11) at levels similar than wild-type HIV and did not induce the activation of the IV-9 clone (Fig.…”

Section: Hiv Viral Proteins Nef and Env Do Not Significantly Impact Ementioning

confidence: 86%

“…Through the action of accessory viral proteins such as Nef, HIV developed multiple strategies to manipulate the trafficking of cellular receptors and vesicles (68). In particular, Nef induces a strong accumulation of surface-immature MHC-II molecules characterized by a reduced capacity to present exogenous peptide to Ag-specific CD4 + T cells (61).…”

Section: Hiv Viral Proteins Nef and Env Do Not Significantly Impact Ementioning

confidence: 99%

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HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

Coulon

Richetta

Rouers

et al. 2016

The Journal of Immunology

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It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II–restricted endogenous viral Ags to HIV-specific (HS) CD4+ T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4+ T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4+ T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II–restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4+ T cell responses, thus favoring an endogenous MHC-II–restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4+ T cell responses. These findings will help in designing novel strategies to activate HS CD4+ T cells that are required for CTL activation/maintenance and B cell maturation.

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Section: Hiv Viral Proteins Nef and Env Do Not Significantly Impact Ementioning

confidence: 86%

Section: Hiv Viral Proteins Nef and Env Do Not Significantly Impact Ementioning

confidence: 99%

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

Coulon

Richetta

Rouers

et al. 2016

The Journal of Immunology

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“…Elle est associée à la face interne de la membrane plasmique. Nef ne possède pas d'activité enzymatique mais exerce de multiples fonctions (pour une revue détail-lée voir [3]), dont les principales sont liées à ses capacités d'interaction avec les machineries de trafic et de signalisation intracellulaire [4] (➜). Un des premiers effets de Nef à avoir été décrit est la diminution de l'expression, à la surface cellulaire, de CD4, le récepteur du VIH, et des molécules du complexe majeur d'histocompatibilité de classe I (CMH-I).…”

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“…Un des premiers effets de Nef à avoir été décrit est la diminution de l'expression, à la surface cellulaire, de CD4, le récepteur du VIH, et des molécules du complexe majeur d'histocompatibilité de classe I (CMH-I). Il a ensuite été montré que Nef pouvait modifier l'expression membranaire de nombreuses protéines [3]. Une autre propriété importante de Nef, décrite il y a une vingtaine d'années, est sa capacité à augmenter l'infectivité des virions produits par la cellule infectée [3].…”

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La mystérieuse cible de la protéine virale Nef identifiée : les protéines SERINC3 et SERINC5

Chauveau

2016

Med Sci (Paris)

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Structural studies and SH3 domain binding properties of a human antiviral salivary proline‐rich peptide

Righino¹,

Pirolli²,

Radicioni³

et al. 2016

Biopolymers

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Human saliva contains hundreds of small proline-rich peptides originated by the proteolytic cleavage of the salivary basic Proline-Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti-HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline-II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c-Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016.

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The activity of Nef on HIV-1 infectivity

Cited by 75 publications

References 167 publications

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

La mystérieuse cible de la protéine virale Nef identifiée : les protéines SERINC3 et SERINC5

Structural studies and SH3 domain binding properties of a human antiviral salivary proline‐rich peptide

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