ArticlePloS one2011
The identification of a small molecule compound that reduces HIV-1 Nef-mediated viral infectivity enhancement.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- M-Sec promotes the production of infectious HIV-1 virus through the exocyst complex in macrophages.PLoS pathogens · 2026Article
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- Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated KBritish journal of pharmacology · 2020Article
- HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.AIDS research and therapy · 2017Review
- Development and validation of a high-content bimolecular fluorescence complementation assay for small-molecule inhibitors of HIV-1 Nef dimerization.Journal of biomolecular screening · 2014Article
- Small molecule inhibitors of the HIV-1 virulence factor, Nef.Drug discovery today. Technologies · 2013Review
- Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen.Retrovirology · 2013Article
- Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins.Microbes and infection · 2013Article
- Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity.Chemistry & biology · 2013Article
- Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix.Retrovirology · 2012Article
- Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function.Retrovirology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nef is a multifunctional HIV-1 protein that accelerates progression to AIDS, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood. Here, we show that the small molecule compound 2c reduces Nef-mediated viral infectivity enhancement. When added to viral producer cells, 2c did not affect the efficiency of viral production itself. However, the infectivity of the viruses produced in the presence of 2c was significantly lower than that of control viruses. Importantly, an inhibitory effect was observed with Nef(+) wild-type viruses, but not with viruses produced in the absence of Nef or in the presence of proline-rich PxxP motif-disrupted Nef, both of which displayed significantly reduced intrinsic infectivity. Meanwhile, the overexpression of the SH3 domain of the tyrosine kinase Hck, which binds to a PxxP motif in Nef, also reduced viral infectivity. Importantly, 2c inhibited Hck SH3-Nef binding, which was more marked when Nef was pre-incubated with 2c prior to its incubation with Hck, indicating that both Hck SH3 and 2c directly bind to Nef and that their binding sites overlap. These results imply that both 2c and the Hck SH3 domain inhibit the interaction of Nef with an unidentified host protein and thereby reduce Nef-mediated infectivity enhancement. The first inhibitory compound 2c is therefore a valuable chemical probe for revealing the underlying molecular mechanism by which Nef enhances the infectivity of HIV-1.
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