1887

Abstract

We reported previously that Pin1 facilitates human immunodeficiency virus type 1 (HIV-1) uncoating by interacting with the capsid core through the phosphorylated Ser-Pro motif. However, the specific kinase responsible for Ser phosphorylation has remained unknown. Here, we showed that virion-associated extracellular signal-regulated kinase 2 (ERK2) phosphorylates Ser. The characterization of immature virions produced by exposing chronically HIV-1-infected CEM/LAV-1 cells to 10 µM saquinavir indicated that Ser is phosphorylated after the initiation of Pr55 processing. Furthermore, a mass spectrometry-based kinase assay demonstrated that ERK2 specifically phosphorylated the Ser residue in the Ser-Pro motif-containing substrate. The treatment of CEM/LAV-1 cells with the ERK2 inhibitor sc-222229 decreased the Ser phosphorylation level inside virions, and virus partially defective in Ser phosphorylation showed impaired reverse transcription and attenuated replication owing to attenuated Pin1-dependent uncoating. Furthermore, the suppression of ERK2 expression by RNA interference in CEM/LAV-1 cells resulted in suppressed ERK2 packaging inside virions and decreased the Ser phosphorylation level inside virions. Interestingly, the ERK2-packaging-defective virus showed impaired reverse transcription and attenuated HIV-1 replication. Taken together, these findings provide insights into the as-yet-obscure processes in Pin1-dependent HIV-1 uncoating.

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2014-05-01
2021-03-08
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