Abstract:
:Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes.
journal_name
Virologyjournal_title
Virologyauthors
Esposito AM,Cheung P,Swartz TH,Li H,Tsibane T,Durham ND,Basler CF,Felsenfeld DP,Chen BKdoi
10.1016/j.virol.2015.10.013subject
Has Abstractpub_date
2016-03-01 00:00:00pages
6-16eissn
0042-6822issn
1096-0341pii
S0042-6822(15)00441-9journal_volume
490pub_type
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