Abstract
The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Active Transport, Cell Nucleus / genetics
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Animals
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Antiviral Restriction Factors
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Aotidae
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Capsid Proteins / genetics*
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Capsid Proteins / metabolism
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Carrier Proteins / pharmacology
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Cell Division
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Cell Line
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Cyclophilin A / pharmacology*
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HIV-1 / drug effects
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HIV-1 / genetics*
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HIV-1 / metabolism*
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Humans
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Macrophages / drug effects*
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Macrophages / virology*
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Microbial Sensitivity Tests
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Mutation*
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RNA-Directed DNA Polymerase / metabolism
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Reverse Transcriptase Inhibitors / pharmacology
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Tripartite Motif Proteins
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Ubiquitin-Protein Ligases
Substances
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Antiviral Restriction Factors
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Capsid Proteins
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Carrier Proteins
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Reverse Transcriptase Inhibitors
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Tripartite Motif Proteins
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TRIM5 protein, human
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Ubiquitin-Protein Ligases
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RNA-Directed DNA Polymerase
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Cyclophilin A